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Sexual Precocity in a 16-Month-Old
2 e- M" Q: q3 g. G; `/ x# Y0 h+ E2 qBoy Induced by Indirect Topical- k: r! S: d6 S) e
Exposure to Testosterone
4 Z3 ^. o6 J2 cSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,26 t+ p" V6 }: T$ S4 T B! N
and Kenneth R. Rettig, MD1; o. _! G) {4 F/ `$ @/ Q
Clinical Pediatrics5 a/ g! A) \$ @' x# W* t: k& A4 [
Volume 46 Number 6
$ C1 z2 M# {. [July 2007 540-5439 ^! X& l+ G+ i% ?% [& l
© 2007 Sage Publications
' |- K% Y% ~; T) d# v6 J3 q10.1177/0009922806296651
- l& b8 c- z/ e8 Z' {9 shttp://clp.sagepub.com
1 m s' k O/ p: W1 fhosted at
$ y. `7 `% r6 P# ?1 X, P! q1 @http://online.sagepub.com, _( @/ p Z( K. G
Precocious puberty in boys, central or peripheral,% P& |1 T; t. _$ b1 o, b
is a significant concern for physicians. Central+ h; t- `; }2 [8 A, Z4 H
precocious puberty (CPP), which is mediated
2 P$ M1 e6 z! x ?through the hypothalamic pituitary gonadal axis, has
) k: j! n& e8 P) i! ?a higher incidence of organic central nervous system
$ A: z2 `# x& `' ~ Vlesions in boys.1,2 Virilization in boys, as manifested
3 K d6 w. N' c' n0 s7 ^3 S4 m4 tby enlargement of the penis, development of pubic- z$ Z/ H, m' Q( P9 N; H
hair, and facial acne without enlargement of testi-. k/ O+ T+ a; O; x
cles, suggests peripheral or pseudopuberty.1-3 We0 M0 ^- g- D1 q4 v+ @# m, w7 g
report a 16-month-old boy who presented with the2 P2 ~8 ^: j& x3 g
enlargement of the phallus and pubic hair develop-
8 I* [1 Z. ]; h6 nment without testicular enlargement, which was due) } c- F9 L! u7 e5 s# Q3 ?0 Q
to the unintentional exposure to androgen gel used by
/ J2 @3 H) [4 C$ T) N2 C4 Xthe father. The family initially concealed this infor-
6 Q, q% n' v6 Y+ Q% u. U% j/ i5 @mation, resulting in an extensive work-up for this
& a6 Q B* ~5 b. i& [, E: J) Dchild. Given the widespread and easy availability of
6 V) P9 f, q! K: r5 r3 Dtestosterone gel and cream, we believe this is proba-8 x4 [0 J( a- y+ {: D
bly more common than the rare case report in the1 `; g( B0 N5 ?2 x; G4 j6 P
literature.4
0 e( Z6 Q- v, i- @# o9 e# _Patient Report
2 B/ U1 ]$ v( [A 16-month-old white child was referred to the/ ^# s# o' e6 v |5 m4 v
endocrine clinic by his pediatrician with the concern
- w- j' e0 L# ?: D. m) Y6 [4 q; Kof early sexual development. His mother noticed
/ X7 P+ O- H5 c) ~# v0 `2 plight colored pubic hair development when he was
% I3 S. C: x' CFrom the 1Division of Pediatric Endocrinology, 2University of
+ |/ r$ P& m+ u WSouth Alabama Medical Center, Mobile, Alabama.
8 I% `- H4 q8 ]* X3 Y, oAddress correspondence to: Samar K. Bhowmick, MD, FACE,
; Z! C% g3 q1 |9 E$ dProfessor of Pediatrics, University of South Alabama, College of0 J9 T3 Z+ R) S: x: i) E) l
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;) E7 A0 @- Y/ r6 O3 `( C% [) w
e-mail: [email protected].
e# d/ ?% r- z& P9 ], s1 x8 Uabout 6 to 7 months old, which progressively became
; I/ K( ~. T# ]4 @; jdarker. She was also concerned about the enlarge-
. E. J8 y# b6 r% ]ment of his penis and frequent erections. The child; n2 h3 y* y$ j, P- P
was the product of a full-term normal delivery, with
0 J" s" I" W l! aa birth weight of 7 lb 14 oz, and birth length of0 H6 f, ` P! R- v' z" U
20 inches. He was breast-fed throughout the first year/ a g Q# v3 T: c4 r+ O$ h
of life and was still receiving breast milk along with- D' t8 w1 Z8 I0 d$ Z
solid food. He had no hospitalizations or surgery,
# S) h7 |1 Y$ [6 i# z3 Y% Rand his psychosocial and psychomotor development
% J m4 {) X( k$ e M' Pwas age appropriate.' z5 [: J1 u9 ]& Q# C/ C9 v, r
The family history was remarkable for the father,
. d' f. ^3 W/ p! c! rwho was diagnosed with hypothyroidism at age 16,* }1 m' o1 v1 Y7 H! v
which was treated with thyroxine. The father’s) Z& Q5 q% E: @5 f2 K7 W
height was 6 feet, and he went through a somewhat! ~& J: \* D! G, G* n9 T7 z1 w
early puberty and had stopped growing by age 14.5 u& C8 c/ B2 u1 P
The father denied taking any other medication. The& S: R7 `% W9 Z \' t; E
child’s mother was in good health. Her menarche
" R9 o- @0 p/ E1 [( ^) [was at 11 years of age, and her height was at 5 feet
6 ]& z2 R0 H! h) b. o5 inches. There was no other family history of pre-
' B) d9 r$ f0 p% C9 Scocious sexual development in the first-degree rela-! A. B0 P `" C
tives. There were no siblings.
5 l1 _; q: c" p; \Physical Examination
9 d, f, h! r3 BThe physical examination revealed a very active, r- [8 g" A* E/ b g5 E1 d' d
playful, and healthy boy. The vital signs documented
2 Q1 l8 P+ p9 \; M8 Ta blood pressure of 85/50 mm Hg, his length was
5 W# r+ n( E) p6 v5 R3 T90 cm (>97th percentile), and his weight was 14.4 kg2 x5 |. a- o/ r5 T: m4 m+ m
(also >97th percentile). The observed yearly growth+ P$ A- q- s2 m$ |" `5 E( O1 ?
velocity was 30 cm (12 inches). The examination of
! n3 w2 c8 C. l' Wthe neck revealed no thyroid enlargement.
1 y" t- T! P. J: k7 q% H7 jThe genitourinary examination was remarkable for
' c% M$ c+ L K( k: b wenlargement of the penis, with a stretched length of
4 S' C) T% Q* u7 H7 Z8 cm and a width of 2 cm. The glans penis was very well
9 D E- W0 j/ \& i7 fdeveloped. The pubic hair was Tanner II, mostly around: \. i: X2 b. b+ W `& y
540
: P, S _( i: g4 v8 g2 Hat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& {% y0 _ ]/ j! o8 Kthe base of the phallus and was dark and curled. The: G- z) T" i& U
testicular volume was prepubertal at 2 mL each.2 {: }' I# k/ y
The skin was moist and smooth and somewhat
- [ {6 e' L, z; |oily. No axillary hair was noted. There were no, r% T( v9 T( F& L/ j" A
abnormal skin pigmentations or café-au-lait spots.
' f& W- m+ G. c( sNeurologic evaluation showed deep tendon reflex 2+* V: o) s g, b. X
bilateral and symmetrical. There was no suggestion% ?' @# l' T) s- o
of papilledema./ l% c K3 C z6 G1 E0 Q3 p4 K' [- P
Laboratory Evaluation' m( b, M V: }+ S0 V! ~
The bone age was consistent with 28 months by
$ }1 N1 H5 L' N4 \1 E) G, f# }6 susing the standard of Greulich and Pyle at a chrono-4 b9 J/ p. g1 i" j+ H' z8 Y
logic age of 16 months (advanced).5 Chromosomal
. |9 C- ~5 j9 f3 qkaryotype was 46XY. The thyroid function test
7 U0 h9 M7 x2 b0 d$ @2 zshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
- v' u) e) L3 Y+ D0 Glating hormone level was 1.3 µIU/mL (both normal).
6 F* V) E+ Y ?4 X7 [The concentrations of serum electrolytes, blood8 Q& h% j# @9 B) o8 U$ m0 \
urea nitrogen, creatinine, and calcium all were
' m, c7 N9 w0 vwithin normal range for his age. The concentration- w7 n: W: L( @
of serum 17-hydroxyprogesterone was 16 ng/dL Q! W6 L& q) T) P4 O
(normal, 3 to 90 ng/dL), androstenedione was 20
1 A; q" W( I4 n& ^4 wng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( i5 c. s; |7 D% O: ^) ^! Bterone was 38 ng/dL (normal, 50 to 760 ng/dL),. f/ l! n! E; I$ R& o
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
! X0 c$ I% m* m. P49ng/dL), 11-desoxycortisol (specific compound S)) A! s4 `) C; T' k: H: \( P$ m
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-) D1 Q" Z! T' Y" V6 |5 _1 s& u
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
0 ^, B/ q: m+ vtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
9 C( ]. i1 J! N4 P: M' c5 \/ fand β-human chorionic gonadotropin was less than
- n+ u/ }/ w" O/ O, P. ~5 mIU/mL (normal <5 mIU/mL). Serum follicular
8 S7 c9 N# q4 q6 ^/ tstimulating hormone and leuteinizing hormone0 u# {& x$ N2 E- }1 c1 m
concentrations were less than 0.05 mIU/mL
$ L6 C4 o# J, k: C5 R1 r: H, l(prepubertal).0 y. \9 n; N1 P
The parents were notified about the laboratory) m6 ]! H3 i# Y! [* r% d
results and were informed that all of the tests were- v# q: Y# s/ X7 r* t3 g
normal except the testosterone level was high. The. K5 O3 [7 W) g' n2 @, k' ?
follow-up visit was arranged within a few weeks to$ }9 t+ }* p2 u6 _$ _
obtain testicular and abdominal sonograms; how-
; r* S, g; \* M1 m" never, the family did not return for 4 months.
0 h% ^; L1 p! gPhysical examination at this time revealed that the) y. y5 }( R4 d k" b' v8 `# x
child had grown 2.5 cm in 4 months and had gained' @, E9 x, a0 o7 L2 ?+ e
2 kg of weight. Physical examination remained
8 ^5 D* ^) N( W1 `unchanged. Surprisingly, the pubic hair almost com-
$ Y0 A3 U: z- l lpletely disappeared except for a few vellous hairs at
1 _% [4 k! R: b. u6 K, a& Kthe base of the phallus. Testicular volume was still 2' ^! E3 Y v( E+ z, r! q
mL, and the size of the penis remained unchanged.9 F/ p) h; U, @" S' l( l
The mother also said that the boy was no longer hav-6 A; _; e# o* d
ing frequent erections.
/ A/ c% t$ I1 }% z) x MBoth parents were again questioned about use of5 G7 _- f5 X& k4 U T2 v/ a2 g8 b
any ointment/creams that they may have applied to
, l/ y& H- ?- U8 M8 D; W/ s+ C" sthe child’s skin. This time the father admitted the9 m% F# ~- O" p% V
Topical Testosterone Exposure / Bhowmick et al 5411 d* A8 W% e$ V
use of testosterone gel twice daily that he was apply-+ f4 z9 @! v- \- u2 v
ing over his own shoulders, chest, and back area for
* w, F/ y' s6 w+ y; L: ba year. The father also revealed he was embarrassed
5 z( d7 r3 @9 t+ f/ g6 Z1 Ato disclose that he was using a testosterone gel pre-
- L% U- F: d4 v3 L; Tscribed by his family physician for decreased libido: l& W- B8 E# ?3 Z8 i& X$ A
secondary to depression.
4 S1 k- Z Y! S* H: l/ _+ `) ~: Q }The child slept in the same bed with parents.$ s/ \1 V9 }7 U
The father would hug the baby and hold him on his" S% k3 y) _' I
chest for a considerable period of time, causing sig-2 D8 d. i$ k: w% h2 K9 F K
nificant bare skin contact between baby and father.
& Q8 C0 A4 j8 b3 B2 j2 k) DThe father also admitted that after the phone call,
. w O) P- Z, S! ]' p+ v! ~when he learned the testosterone level in the baby4 ?* [* K4 S# N% x; l
was high, he then read the product information
$ O% H% S) p3 j2 Ypacket and concluded that it was most likely the rea-% c" W8 h% x) j4 @% G8 T
son for the child’s virilization. At that time, they
7 ]' s. e s% p2 B, j. ~decided to put the baby in a separate bed, and the1 s9 g! o1 d! x( x
father was not hugging him with bare skin and had$ l4 \8 A- ?7 {6 @) E
been using protective clothing. A repeat testosterone
* y P% J7 ]8 R a, m H4 itest was ordered, but the family did not go to the
, I" @, @; {, {5 f, w8 T/ S9 Hlaboratory to obtain the test.
5 L6 p( J2 N z. V% {Discussion9 @7 P( ]" J3 T2 z0 K+ C1 o5 F" Y
Precocious puberty in boys is defined as secondary5 w |, Z% B# H3 ~+ p: T6 z
sexual development before 9 years of age.1,4, B- m7 x* H m7 ]
Precocious puberty is termed as central (true) when: i- c8 i4 C6 t0 [
it is caused by the premature activation of hypo-8 q7 }; z6 l) ?( X- [" H3 }
thalamic pituitary gonadal axis. CPP is more com-
% J( B, R$ \+ \8 bmon in girls than in boys.1,3 Most boys with CPP
3 c4 N$ L6 Y! E' Jmay have a central nervous system lesion that is: _2 v9 T" H+ J. C
responsible for the early activation of the hypothal-
. O/ l; y: K+ i1 uamic pituitary gonadal axis.1-3 Thus, greater empha-* X. ^5 U: A+ L1 I( T+ _7 O
sis has been given to neuroradiologic imaging in
! M: B8 @0 n6 f3 c8 l( j9 mboys with precocious puberty. In addition to viril-
+ D2 D5 V# Q8 U3 e; u, s: Hization, the clinical hallmark of CPP is the symmet-- O$ ^' K$ E, H8 \7 _
rical testicular growth secondary to stimulation by* @8 Y) V; |9 b& b
gonadotropins.1,30 l4 G* ^" q1 d5 p7 \* j8 r8 I, b
Gonadotropin-independent peripheral preco-6 n O/ c# K7 D8 c6 W
cious puberty in boys also results from inappropriate
1 C/ t r* m ^, nandrogenic stimulation from either endogenous or
4 M+ t! f4 ]6 w' ?# Oexogenous sources, nonpituitary gonadotropin stim-: t$ O; K4 o0 U: i. Z( K5 C* n* }
ulation, and rare activating mutations.3 Virilizing
& F Y l5 o, x& r% ~congenital adrenal hyperplasia producing excessive
8 _! K2 G/ V- `; Y9 H: }adrenal androgens is a common cause of precocious: D L* v n/ U# p; ^" _4 t2 l
puberty in boys.3,4
4 ]3 T* e, p3 z0 wThe most common form of congenital adrenal5 p8 G8 e* |2 q0 S5 k
hyperplasia is the 21-hydroxylase enzyme deficiency.
9 O* C% J9 R! [9 o* xThe 11-β hydroxylase deficiency may also result in
7 u, i3 w* G3 F7 H5 A( A& lexcessive adrenal androgen production, and rarely,
* Y' q# e0 K/ Y4 C( f% a+ Fan adrenal tumor may also cause adrenal androgen
1 [# |8 f5 ]6 Z" X5 Hexcess.1,3: K- C9 b) Z: q U
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
# O( B# x. l( Y+ u, d& s1 t542 Clinical Pediatrics / Vol. 46, No. 6, July 20071 O& _ j' w4 X; w2 @# O) p: H- a3 a
A unique entity of male-limited gonadotropin-
( m/ J! ^- A/ d' m- Jindependent precocious puberty, which is also known9 @0 r2 g; q0 f- ?; v
as testotoxicosis, may cause precocious puberty at a
2 z$ Q# P) U- gvery young age. The physical findings in these boys# M g# U* M' i$ l% n) ~
with this disorder are full pubertal development,
9 N, X6 k- ?5 ~; c) j# A$ H/ Kincluding bilateral testicular growth, similar to boys( I1 |5 m6 P; A
with CPP. The gonadotropin levels in this disorder
# v- [$ `6 O! u, `! [are suppressed to prepubertal levels and do not show
' s% M: a# T* a8 W( y6 z: k$ Rpubertal response of gonadotropin after gonadotropin-3 G& L( j+ m* M9 x" p ]
releasing hormone stimulation. This is a sex-linked" @9 b2 W5 ~8 A c. z
autosomal dominant disorder that affects only) u+ {# Z# `5 X; g. {( F5 B
males; therefore, other male members of the family
) b4 v! A) w6 }3 amay have similar precocious puberty.3
h% T. |, o- K$ zIn our patient, physical examination was incon-, ]! L% m* ?3 N4 y8 U$ C) T( t
sistent with true precocious puberty since his testi-" w) {/ s) J* x' J6 n, ~
cles were prepubertal in size. However, testotoxicosis
" M |1 N. N7 \. B8 mwas in the differential diagnosis because his father: K& ~6 l+ ]( K I* w
started puberty somewhat early, and occasionally,
" U8 V1 g) Y, s! H/ ftesticular enlargement is not that evident in the
" e! h; t2 K3 e0 T" |+ fbeginning of this process.1 In the absence of a neg-' ]& D, z4 `, g D7 h6 q
ative initial history of androgen exposure, our0 q/ y$ ~9 ~. u
biggest concern was virilizing adrenal hyperplasia,
' d4 [2 k K/ _% u7 ~1 heither 21-hydroxylase deficiency or 11-β hydroxylase
9 j5 k, ^8 [$ H w5 C+ ndeficiency. Those diagnoses were excluded by find-
6 t5 K1 C4 P; _$ j" aing the normal level of adrenal steroids.* Z, w1 y2 T! n5 w7 |7 d H
The diagnosis of exogenous androgens was strongly
1 I1 k8 H7 F7 v ^3 \( o* ~1 B& W, esuspected in a follow-up visit after 4 months because
4 [, G$ H0 L0 P) i) M! N8 Lthe physical examination revealed the complete disap-4 y. j/ V8 d' m) m0 x' R5 Y
pearance of pubic hair, normal growth velocity, and
( Z% k$ g6 o2 Ddecreased erections. The father admitted using a testos-
3 A, o, _8 j9 c8 F( W3 \) iterone gel, which he concealed at first visit. He was
. Z9 O: P E& w2 F! d7 i' b" Pusing it rather frequently, twice a day. The Physicians’
5 o. R4 z. c; |Desk Reference, or package insert of this product, gel or/ O# {) ~- s* m) c, L8 A z
cream, cautions about dermal testosterone transfer to
' x8 c3 j7 A8 o2 z: L7 O- | Eunprotected females through direct skin exposure.
/ e( j% {( g4 r8 `8 c* R+ b& tSerum testosterone level was found to be 2 times the
, c \/ l& f- v/ X+ h7 @( jbaseline value in those females who were exposed to
! g6 p3 U: c |& \. Geven 15 minutes of direct skin contact with their male& j( n" M" b0 ?' O7 c. s9 b7 c5 b
partners.6 However, when a shirt covered the applica- n& H8 D: m/ [! T' z0 ~2 w4 f% i
tion site, this testosterone transfer was prevented.- O" d; L8 o, z8 r8 }0 v
Our patient’s testosterone level was 60 ng/mL,$ [; q8 y* l' x, o1 N% {" T
which was clearly high. Some studies suggest that X5 m, z) D7 H0 s8 F* X
dermal conversion of testosterone to dihydrotestos-
: t3 I* g9 e7 ~- t/ }terone, which is a more potent metabolite, is more
4 X7 l1 \7 ^" tactive in young children exposed to testosterone% B- x0 B: O+ |0 ]8 ~, K
exogenously7; however, we did not measure a dihy-9 P6 Y9 }2 P. Y& r h
drotestosterone level in our patient. In addition to
3 s1 n* b7 A+ |* O5 ?7 {# jvirilization, exposure to exogenous testosterone in6 M0 k( f% p; [! ~2 z! C$ B
children results in an increase in growth velocity and3 q' Y1 g- e/ ?9 k+ Q
advanced bone age, as seen in our patient.
$ v: _- F4 N: VThe long-term effect of androgen exposure during
# `& H/ t. b! {% [early childhood on pubertal development and final: v! Y& x! r0 Z9 X- z8 x8 M& T" n
adult height are not fully known and always remain) e4 g6 o% Z, G+ B) E
a concern. Children treated with short-term testos-2 E4 y A! D) r8 c! e
terone injection or topical androgen may exhibit some
/ q% [* P2 G8 ?+ y* s: B6 nacceleration of the skeletal maturation; however, after
4 S% V3 r+ Y5 O! J/ Rcessation of treatment, the rate of bone maturation8 O7 v4 a- e3 T3 b' E& q
decelerates and gradually returns to normal.8,94 C+ n9 b2 @. A' W. u' V
There are conflicting reports and controversy
" K w$ ~- C9 ^over the effect of early androgen exposure on adult
* K& E) ~2 [0 U% M. G4 P6 A4 g4 Gpenile length.10,11 Some reports suggest subnormal
0 }2 y1 Y) z3 J: ?5 Gadult penile length, apparently because of downreg-+ ~, q" N# @ h2 x! L
ulation of androgen receptor number.10,12 However,
2 z# R! a" e; |1 F; E( o0 y4 ISutherland et al13 did not find a correlation between) F- `3 y0 V# q' r
childhood testosterone exposure and reduced adult
' B# j) V+ v% {- Spenile length in clinical studies.% ?7 z0 a1 d8 `8 b( K& J" P& l* @
Nonetheless, we do not believe our patient is
: @# w: ^: t+ G' B/ m: zgoing to experience any of the untoward effects from
& N, B! g+ @9 S y5 \/ |1 Rtestosterone exposure as mentioned earlier because7 z' ^ C( z6 S f$ L9 C
the exposure was not for a prolonged period of time.1 k0 {. z/ {5 T) @
Although the bone age was advanced at the time of8 P1 i$ O: t8 J+ c% F
diagnosis, the child had a normal growth velocity at4 P( B: }4 O0 a* Z8 B1 v
the follow-up visit. It is hoped that his final adult
+ F/ ?; w1 P' r, Theight will not be affected.' ~. H5 j3 Q5 Z. E1 @
Although rarely reported, the widespread avail-4 q" S! n9 @9 ?
ability of androgen products in our society may0 d4 } i) H+ |8 j; O
indeed cause more virilization in male or female% |9 I; b- [ O4 q6 {- f7 {0 m6 Q
children than one would realize. Exposure to andro-3 K: F+ X9 X9 p: H# Q1 O. b
gen products must be considered and specific ques-: T! _7 R3 p8 i1 M8 i( {
tioning about the use of a testosterone product or: i+ P0 c- p2 s4 N- s4 s
gel should be asked of the family members during
# H/ x9 D" V5 [the evaluation of any children who present with vir-
6 N& t5 l( ^! T3 I* u1 yilization or peripheral precocious puberty. The diag-
( g# n% ~6 G& R& S& Lnosis can be established by just a few tests and by6 E8 Y. @1 \# V) j
appropriate history. The inability to obtain such a7 r' @& D9 [3 H
history, or failure to ask the specific questions, may* x N; X; P1 k. t) M% j5 p* T
result in extensive, unnecessary, and expensive5 V% k" x! B3 b
investigation. The primary care physician should be& T) S1 o. W& l* j
aware of this fact, because most of these children: r. L" b ^+ a+ g
may initially present in their practice. The Physicians’
' F2 r z, B- Q: V9 w; bDesk Reference and package insert should also put a
) \, I6 R2 v2 v' q4 P' s) v$ pwarning about the virilizing effect on a male or4 m% O9 v! M, q* V
female child who might come in contact with some-* `6 g& u9 t# \% p' T
one using any of these products.
: E5 v8 Z. ^, v2 jReferences
, q; z0 f" d5 S, ~1. Styne DM. The testes: disorder of sexual differentiation
# j8 j/ ^. U( \ F" E Q; ]and puberty in the male. In: Sperling MA, ed. Pediatric2 k6 X" E7 K- x& n
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
5 j" R4 j- J6 V2 Q% ]+ k3 }+ e2002: 565-628.- S; }: X- m! h0 c& h1 M1 h$ h
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious4 ~; W% C: E `8 @9 i( l; j8 |
puberty in children with tumours of the suprasellar pineal |
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