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Sexual Precocity in a 16-Month-Old
- R( j- {! Q2 P& R# oBoy Induced by Indirect Topical
' A6 z- u+ U! L9 [Exposure to Testosterone
9 z+ _; R A: F6 E5 i' k8 R2 @# c* `Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
! R9 S( U$ H- `5 ]' \4 ]and Kenneth R. Rettig, MD1
) [: \# L5 j" K" ]Clinical Pediatrics
% I! H2 Q6 v# H9 ?Volume 46 Number 6! j3 F( o9 j& d
July 2007 540-543
" Q9 r9 b Z3 Z+ B© 2007 Sage Publications
. Y+ h. H8 E* C% d' l' T- \10.1177/0009922806296651
8 Z+ N0 l l& M1 @2 C- D& b! ehttp://clp.sagepub.com. A7 z1 O( A' P% s1 F6 e& K
hosted at
4 O+ t- \, m, g( I+ w a Dhttp://online.sagepub.com
: D/ ?; p7 r2 a+ G! A7 HPrecocious puberty in boys, central or peripheral,
3 U* `1 P( f4 _; H2 x k/ ?is a significant concern for physicians. Central
" G; Y# V3 K* q3 m" F' Kprecocious puberty (CPP), which is mediated2 F- d; i8 t1 m& ] ?3 t e1 ?" |
through the hypothalamic pituitary gonadal axis, has
0 W: w) X% }; ~8 ~2 Q3 S' r# Ha higher incidence of organic central nervous system$ }9 b" H1 b, ~; ?- e" f
lesions in boys.1,2 Virilization in boys, as manifested
' u+ {6 g% `8 xby enlargement of the penis, development of pubic
$ [3 _- k! g* Hhair, and facial acne without enlargement of testi-* }5 _1 n% O$ T; _
cles, suggests peripheral or pseudopuberty.1-3 We7 C2 p% j& \( {0 Z3 ]6 Z9 Y
report a 16-month-old boy who presented with the
/ \8 u; Q! N5 P3 H$ Benlargement of the phallus and pubic hair develop-
/ ^6 ^# J y6 [; T8 E+ E' s5 Wment without testicular enlargement, which was due
3 U/ q- s/ _7 R$ T! ato the unintentional exposure to androgen gel used by5 V/ n5 ?) [6 c1 \. d
the father. The family initially concealed this infor-
7 w- b% v4 v5 ]6 Jmation, resulting in an extensive work-up for this& [ i% E& ]2 e2 {4 p/ G
child. Given the widespread and easy availability of
9 U! w* l/ `) B! s* l$ d2 htestosterone gel and cream, we believe this is proba-' _& F; a8 W* [: Q8 e
bly more common than the rare case report in the- P8 {$ e' J6 I; @
literature.4, ?$ C# {, |* g- N9 E
Patient Report$ a) ?. X9 [. v$ b
A 16-month-old white child was referred to the! M: \+ S. b, y* C
endocrine clinic by his pediatrician with the concern
) V- m& @* |/ k! Q/ G# y, K0 _of early sexual development. His mother noticed, K: w) ^9 d) c5 F; I0 L
light colored pubic hair development when he was
$ c9 O3 }/ K: s8 ?From the 1Division of Pediatric Endocrinology, 2University of
2 l3 u5 [) n: ~& s1 q* h& j' X6 X5 u. HSouth Alabama Medical Center, Mobile, Alabama.6 }; }4 X5 Y5 j4 `
Address correspondence to: Samar K. Bhowmick, MD, FACE,2 v9 F& P. r: o+ G) k- M
Professor of Pediatrics, University of South Alabama, College of
% d9 @% \0 n* D" ?Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
w( o5 t9 v8 z2 z6 |% e9 B+ Ke-mail: [email protected].5 W' t- Z; X; w8 ?
about 6 to 7 months old, which progressively became( M% @/ `; ?, ]$ K6 Q$ H1 C
darker. She was also concerned about the enlarge-
3 |+ b O! A5 lment of his penis and frequent erections. The child
6 O. j3 n* s- i# n8 J$ K0 {was the product of a full-term normal delivery, with
& N& t: a: P& R5 Ka birth weight of 7 lb 14 oz, and birth length of
. F2 c' m+ g; U q* X20 inches. He was breast-fed throughout the first year" a$ A* H {6 w, Z
of life and was still receiving breast milk along with
; s5 ^. s* T) w/ u" H9 |- Q# \solid food. He had no hospitalizations or surgery,$ W( \$ o I8 \ A' Q6 ]# Z1 S
and his psychosocial and psychomotor development# f2 X% T7 l( {; v, p
was age appropriate.
) S" v5 Y8 F. [& n/ WThe family history was remarkable for the father,) ~2 t7 k' T, n' \4 @( p
who was diagnosed with hypothyroidism at age 16,
4 d* ~9 s' ^8 b( p5 Q+ Lwhich was treated with thyroxine. The father’s, q" N7 }; f3 ]
height was 6 feet, and he went through a somewhat
: @, M$ d8 C6 E9 U. ] O' R2 Hearly puberty and had stopped growing by age 14.! C, u3 _" I8 m* C- I3 g
The father denied taking any other medication. The/ U/ c: B% ?1 L' Z- X! ]3 x( L! V
child’s mother was in good health. Her menarche
8 F& z1 K' ]1 O* V8 twas at 11 years of age, and her height was at 5 feet# Z! n' H5 C6 J
5 inches. There was no other family history of pre-
# {2 F, s d/ J5 B) b% {1 Fcocious sexual development in the first-degree rela-
' w0 P' T3 y- X; @7 B* j- o Ctives. There were no siblings. ^, J2 J7 G: T# R( s
Physical Examination2 w/ o4 g# n9 T/ h" [
The physical examination revealed a very active,
: c; h$ @ H! g3 eplayful, and healthy boy. The vital signs documented. K1 [8 q& `! q) J( }
a blood pressure of 85/50 mm Hg, his length was
) X% Q0 ]5 F0 J2 c* v90 cm (>97th percentile), and his weight was 14.4 kg
7 V! G$ b( x1 F% d- I(also >97th percentile). The observed yearly growth
7 ?7 n6 j2 U: X7 Mvelocity was 30 cm (12 inches). The examination of2 t: k, m/ z; P$ ]+ a. z
the neck revealed no thyroid enlargement.6 E- y; }8 C" C3 D( x/ P% q5 h
The genitourinary examination was remarkable for
2 `* c3 c" [# O$ B# wenlargement of the penis, with a stretched length of
( g' K/ J# h( K8 cm and a width of 2 cm. The glans penis was very well
, t& _- r" z) E- O& f( Q7 fdeveloped. The pubic hair was Tanner II, mostly around) d% o: t/ W8 b& B
540- o' x E, g( L, H* o z0 a w6 ^
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; B9 v" u; ^4 c, ?the base of the phallus and was dark and curled. The
% C2 N2 c3 b' Y" y0 p9 {8 c) J9 `6 ytesticular volume was prepubertal at 2 mL each.
7 Z, Q) B! k" _6 a! f# X8 Z- n3 f/ HThe skin was moist and smooth and somewhat
: u4 p) Q, v% h; }, x; \) \oily. No axillary hair was noted. There were no
. T- K( l3 n( t& I& M9 L# mabnormal skin pigmentations or café-au-lait spots., D2 Z% a1 K, q) i8 Q. Q# C) ~* K, J
Neurologic evaluation showed deep tendon reflex 2+
# ?6 J- ~. J$ T0 T9 b0 hbilateral and symmetrical. There was no suggestion5 A3 g3 u6 q4 U: a, ^; Y
of papilledema.
! U" I' t8 N; A& K: P R1 cLaboratory Evaluation) Y; y& R4 {; `) t1 S3 a9 `6 ]
The bone age was consistent with 28 months by
) I8 a: W1 E: Q. J- tusing the standard of Greulich and Pyle at a chrono-$ C, D% `1 I' v D) x: U
logic age of 16 months (advanced).5 Chromosomal4 c8 ]. |, R- M( G( u
karyotype was 46XY. The thyroid function test
$ K9 v5 r3 m& @9 T5 Ishowed a free T4 of 1.69 ng/dL, and thyroid stimu-
0 D% ]4 Y8 R ?# klating hormone level was 1.3 µIU/mL (both normal).
: Y( }3 _' ^2 ^ YThe concentrations of serum electrolytes, blood
5 ^) Q. Q: x9 {8 murea nitrogen, creatinine, and calcium all were; H( {4 j7 L/ A3 G3 M1 x
within normal range for his age. The concentration
, I5 y4 A6 i* E Q3 Vof serum 17-hydroxyprogesterone was 16 ng/dL
7 V, s. X% \/ X( R(normal, 3 to 90 ng/dL), androstenedione was 20
3 p+ O+ d' k' \ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. l* r, \" `, {: K( L
terone was 38 ng/dL (normal, 50 to 760 ng/dL)," }, _9 ]8 A) J) M% v: T3 F B$ T) l% Z
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
( K3 Z* H9 j5 ~) M) U49ng/dL), 11-desoxycortisol (specific compound S)
4 F" O# _9 {8 i3 K: r* a) [5 O6 u' \was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-. d, d7 c5 k0 Q; {0 I
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
( {, _0 J. s& ^- P7 @1 o, u8 t+ atestosterone was 60 ng/dL (normal <3 to 10 ng/dL),, b0 U. ?( J! A, ]# L$ m" ~
and β-human chorionic gonadotropin was less than- C1 \3 Q6 T/ {0 Q1 Y- f
5 mIU/mL (normal <5 mIU/mL). Serum follicular
4 w2 w+ c4 ]# g5 k+ `( Lstimulating hormone and leuteinizing hormone
4 p# c* O5 ]& E' ?3 }% `concentrations were less than 0.05 mIU/mL
, s/ Y9 B' F* S" U* M5 q' s(prepubertal)., h7 B! \) c9 w
The parents were notified about the laboratory
/ p: u V8 p" c8 e+ t5 Q0 B' Presults and were informed that all of the tests were
. Z' X& |0 u2 S1 w( X* G' pnormal except the testosterone level was high. The
: W* d6 i. F* s! g7 `) L! `. pfollow-up visit was arranged within a few weeks to& }1 b- Q( Q+ ^0 D7 ?# z* ?
obtain testicular and abdominal sonograms; how-" U7 ?4 N% `0 r0 w/ J1 C3 K6 x
ever, the family did not return for 4 months.
8 m; s+ [$ }6 p( s; Y7 P$ OPhysical examination at this time revealed that the9 P& A9 ` z3 Z. w, ~
child had grown 2.5 cm in 4 months and had gained# g, Q6 e! i6 n' w
2 kg of weight. Physical examination remained5 T L4 `) r z3 h5 @
unchanged. Surprisingly, the pubic hair almost com-
, s+ x2 h1 ?/ ^! t; [! Ppletely disappeared except for a few vellous hairs at9 D3 q, Q: s# Q" L/ s
the base of the phallus. Testicular volume was still 2
- R; X. O9 N7 ~) [' ~8 PmL, and the size of the penis remained unchanged.
8 W2 j7 L& t/ Q' B) KThe mother also said that the boy was no longer hav-
?$ @" t- l0 f" Z- N( z0 a' l$ Wing frequent erections. V. W( {# E* [0 o) u) d. Y
Both parents were again questioned about use of
% A: B8 X. u1 [- |any ointment/creams that they may have applied to3 R! v F/ t$ j' x- F
the child’s skin. This time the father admitted the/ X$ S3 w2 T" \+ c- y
Topical Testosterone Exposure / Bhowmick et al 541+ k% w2 w% z5 O! _' f) I; ~
use of testosterone gel twice daily that he was apply-3 `" m/ ^) r: l# a. Z4 q8 K
ing over his own shoulders, chest, and back area for
" a } w% y) J/ y& aa year. The father also revealed he was embarrassed
7 K I* u# B6 y; Ito disclose that he was using a testosterone gel pre-
) i( j% ?: i* r: ?8 cscribed by his family physician for decreased libido
% t7 W# G+ T I4 o/ k' H& Wsecondary to depression.5 T% F6 k9 s" [/ v
The child slept in the same bed with parents.
" `: y' e8 Q M( ^' |2 m0 M3 n; ZThe father would hug the baby and hold him on his
3 j, v% X+ `3 j+ rchest for a considerable period of time, causing sig-
$ q4 v" @( p% B: N8 X' w+ inificant bare skin contact between baby and father.
! q! O: ^) \' W E6 E8 LThe father also admitted that after the phone call,: g0 j2 P+ i; s. o
when he learned the testosterone level in the baby
2 c P8 H/ x7 k! \4 q5 @( S* Fwas high, he then read the product information8 n! p' A- v/ u% [" G1 f" N1 m
packet and concluded that it was most likely the rea-
3 ?1 F7 V1 t) A5 j8 {son for the child’s virilization. At that time, they6 d% i$ A I+ E* S
decided to put the baby in a separate bed, and the% s' L3 F) M5 S3 F" s
father was not hugging him with bare skin and had
, y- H$ ~3 u" d3 W1 _5 f1 Dbeen using protective clothing. A repeat testosterone* T" d+ T" T! _ P4 E$ B
test was ordered, but the family did not go to the" t* R5 P: ~% O/ d
laboratory to obtain the test./ ?1 g6 w/ `! D
Discussion `" A2 A' M* ]; \; v
Precocious puberty in boys is defined as secondary0 I5 W- w$ U5 e) N2 s# Y
sexual development before 9 years of age.1,4
1 k2 V% P) m7 g' jPrecocious puberty is termed as central (true) when; q0 r/ P( u a3 ^: S0 p
it is caused by the premature activation of hypo-) _+ e1 _( A1 g0 U* R
thalamic pituitary gonadal axis. CPP is more com-; s$ B5 o; X+ _& ~5 T/ Y
mon in girls than in boys.1,3 Most boys with CPP, `4 z5 z6 }. \& g! q8 h. N2 `
may have a central nervous system lesion that is
1 x/ H. `+ f" P! x- Iresponsible for the early activation of the hypothal-
7 L4 P; ? c. H) O3 oamic pituitary gonadal axis.1-3 Thus, greater empha-
. R1 f* X5 s. k# Y- q/ ~" _sis has been given to neuroradiologic imaging in
. {5 \ w1 ^' y6 g3 pboys with precocious puberty. In addition to viril-
# U. a% c3 N) y; S( gization, the clinical hallmark of CPP is the symmet-' y5 K: \ P) C$ R9 r
rical testicular growth secondary to stimulation by
% `0 w( d E9 m, Cgonadotropins.1,3
: _3 @3 O) Y4 I' `/ Z! pGonadotropin-independent peripheral preco-
. L0 U, Z" i1 |& ~2 r0 [cious puberty in boys also results from inappropriate" s: k. f; A% Y C& Y
androgenic stimulation from either endogenous or% k# v" f7 E# F3 s& t9 H
exogenous sources, nonpituitary gonadotropin stim-
9 X6 N0 {( M) pulation, and rare activating mutations.3 Virilizing
/ V! z5 E% u+ w/ {$ j$ F; ]' Dcongenital adrenal hyperplasia producing excessive! w* K( {& i/ ~" c# d
adrenal androgens is a common cause of precocious; f+ g( P+ K. r3 U3 J; I
puberty in boys.3,4- x$ S3 ^: s% F: c3 q6 J& x' i
The most common form of congenital adrenal _1 C( K, b) V! {
hyperplasia is the 21-hydroxylase enzyme deficiency.
x! J+ U3 |, V: J- j, U2 BThe 11-β hydroxylase deficiency may also result in
* ^; Z6 J$ J% ^+ _0 g4 N& lexcessive adrenal androgen production, and rarely,7 R: u, t" D6 d8 p1 e0 C3 l3 f8 @8 [
an adrenal tumor may also cause adrenal androgen! q v# a8 [9 y# L3 N3 w5 [
excess.1,3
* V- H( P4 [3 n' Z, Z2 ~5 I, Hat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from- j! f& {. `0 Y) v
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
5 P. G1 M1 h, e1 r* NA unique entity of male-limited gonadotropin-
% l2 ]3 \* R5 B' s6 V* T) v& \! bindependent precocious puberty, which is also known
6 `( [8 c( r8 d6 i6 Q+ y C4 xas testotoxicosis, may cause precocious puberty at a( f0 I& q4 ~, j0 r4 p
very young age. The physical findings in these boys) o9 g3 w' J8 a( K2 N) P
with this disorder are full pubertal development,* Z7 x4 z4 L3 S. [3 O
including bilateral testicular growth, similar to boys
. W" z/ H) w7 {& w5 ~+ dwith CPP. The gonadotropin levels in this disorder3 u. ]( F0 s& j1 X7 E
are suppressed to prepubertal levels and do not show
- J; g7 `: p4 G/ w1 Y0 B1 cpubertal response of gonadotropin after gonadotropin-( ~/ ]9 G6 \7 x, |
releasing hormone stimulation. This is a sex-linked
' o* T! ]+ H8 c; O/ K5 t9 x# fautosomal dominant disorder that affects only
' i+ V9 x1 V+ u" C9 Lmales; therefore, other male members of the family
* R/ A7 y+ ?# M" |may have similar precocious puberty.3
6 g# x0 t+ P# B) r9 O# D9 V( R2 HIn our patient, physical examination was incon-" }$ ~$ Q/ C5 I* A/ a
sistent with true precocious puberty since his testi-2 c6 ?. E: C$ j" }' u- S o
cles were prepubertal in size. However, testotoxicosis
" U/ ~% F0 H) l- ^% \ t9 s. Uwas in the differential diagnosis because his father3 o; M4 N9 ^, e! x9 R
started puberty somewhat early, and occasionally,, U: W% v9 X- H
testicular enlargement is not that evident in the
7 Y1 g0 t$ d6 k2 ~* G* bbeginning of this process.1 In the absence of a neg-
& M: I _) T p( B' t) Eative initial history of androgen exposure, our
& e- m# U* {* m- k& ?; jbiggest concern was virilizing adrenal hyperplasia,
9 `4 O1 }4 b1 J% k4 ]2 ~7 E- Jeither 21-hydroxylase deficiency or 11-β hydroxylase
* m4 @' k( N! f9 |9 R( Xdeficiency. Those diagnoses were excluded by find-
( g+ _- G/ G6 m7 _( P' n& wing the normal level of adrenal steroids." [/ ]! b8 J: E
The diagnosis of exogenous androgens was strongly
" n4 s2 F+ c6 q) }! Asuspected in a follow-up visit after 4 months because
* } o3 w8 z: k+ W3 v+ B4 e' E7 Uthe physical examination revealed the complete disap-* E. i" ]" U1 T
pearance of pubic hair, normal growth velocity, and; b/ m3 ~7 s8 Z
decreased erections. The father admitted using a testos-3 U1 B0 C- m: ?: w) U
terone gel, which he concealed at first visit. He was! Q- e3 \# O9 B9 F) M v
using it rather frequently, twice a day. The Physicians’
) Z9 U" k2 ^( [7 J( {+ KDesk Reference, or package insert of this product, gel or; A) M* s b: O( t5 l r s# q
cream, cautions about dermal testosterone transfer to
* L$ a0 m9 z0 |$ zunprotected females through direct skin exposure.
0 T; o) V) c. D9 zSerum testosterone level was found to be 2 times the- i/ v( U7 `4 i
baseline value in those females who were exposed to( l" a; B& X' M6 ] d
even 15 minutes of direct skin contact with their male
. u5 D2 D$ |! j+ i2 }% epartners.6 However, when a shirt covered the applica-4 G# O5 k0 Y, W- e+ P! X
tion site, this testosterone transfer was prevented.
% }) H, K7 i6 I( HOur patient’s testosterone level was 60 ng/mL,$ E: u' c/ L, a& Z8 V
which was clearly high. Some studies suggest that
- q8 i' y: ]; ~% b. i/ Q1 S. A2 Idermal conversion of testosterone to dihydrotestos-+ M: F1 J# r/ G7 h! G7 I4 e8 [
terone, which is a more potent metabolite, is more
' @! j$ {2 F8 bactive in young children exposed to testosterone: l+ n, l; B2 S. G+ F4 x; O
exogenously7; however, we did not measure a dihy-
; p4 i' \. i1 t2 _% T Qdrotestosterone level in our patient. In addition to
* N+ s$ ~+ @& O" l3 _8 nvirilization, exposure to exogenous testosterone in
: e3 S- a; D' f" i5 f+ P2 nchildren results in an increase in growth velocity and
$ Z3 D$ y* Q5 L( G8 ?& e. ^) I5 ?8 jadvanced bone age, as seen in our patient.
+ V7 A" t, X7 TThe long-term effect of androgen exposure during. R- Z- |& E$ R0 y: @. x
early childhood on pubertal development and final3 b4 P) Y& _. k* `( i
adult height are not fully known and always remain! S8 a# p+ n P% z7 L. P" I
a concern. Children treated with short-term testos-1 H; O n, t/ s2 i; B: X
terone injection or topical androgen may exhibit some
$ d7 _4 y/ N7 E1 }2 x, q; r: P- qacceleration of the skeletal maturation; however, after8 L6 ^$ i- I0 h) Q. b
cessation of treatment, the rate of bone maturation
8 N' z/ z6 V. C& }" N! bdecelerates and gradually returns to normal.8,9& w" b- B! W1 J6 s c" c
There are conflicting reports and controversy
' I" Z8 z. S# d2 F! B. e9 t3 K9 L& Mover the effect of early androgen exposure on adult
% W" k! b1 B* |# C; X2 I' {7 gpenile length.10,11 Some reports suggest subnormal, e) u0 Z9 [. A; U% Y
adult penile length, apparently because of downreg-+ p' j `2 V, G/ T8 \9 i
ulation of androgen receptor number.10,12 However,
$ C- D7 Q) D! L+ R) o) g3 p5 WSutherland et al13 did not find a correlation between6 A3 |) o/ I% D: A1 J8 w; C
childhood testosterone exposure and reduced adult
' l; m7 y3 k6 d& \penile length in clinical studies.
; D$ s- u( b. R+ u7 INonetheless, we do not believe our patient is
9 z- q1 x+ G N- b, U3 @3 Y( Cgoing to experience any of the untoward effects from
- P! N9 g- K6 Ztestosterone exposure as mentioned earlier because
$ n8 D+ e/ P7 E* J% W% bthe exposure was not for a prolonged period of time.
7 M z& C. Y2 x' I; eAlthough the bone age was advanced at the time of
3 W% L7 _# S6 S, R6 C. Bdiagnosis, the child had a normal growth velocity at" e% O& n$ [/ k
the follow-up visit. It is hoped that his final adult$ E; l1 ]! w/ F( g, w* H
height will not be affected.& J# Z' y6 L9 Q8 Q u$ D& J
Although rarely reported, the widespread avail-7 ]' J/ B( G4 e
ability of androgen products in our society may
& _% F* Q- ?7 Jindeed cause more virilization in male or female
! P0 i9 A+ x! n% Hchildren than one would realize. Exposure to andro- C5 H, t3 h+ ~$ k' P
gen products must be considered and specific ques-
% ^5 P# b9 N+ }, ^3 l' ~9 [0 ktioning about the use of a testosterone product or, m4 O; U+ C* k6 W
gel should be asked of the family members during% r) V" e' L& [! _9 I! V
the evaluation of any children who present with vir-3 _( n: i) M1 _' b5 d+ B a
ilization or peripheral precocious puberty. The diag-7 M+ H" H& Y4 W
nosis can be established by just a few tests and by
* Q5 o/ L9 }7 a2 Xappropriate history. The inability to obtain such a# {* {) Z5 c, \% t4 U, I/ Z
history, or failure to ask the specific questions, may
* J4 Y0 e' n0 F' g8 yresult in extensive, unnecessary, and expensive+ Y1 h8 F, m4 a0 u/ F
investigation. The primary care physician should be% \8 o. N$ R* d& m' i* q
aware of this fact, because most of these children
* ~) s" N! Q( S% h0 I! b) ?may initially present in their practice. The Physicians’1 t# U; Z& L% S% r; ]
Desk Reference and package insert should also put a
/ X1 h7 G7 S3 D1 k& @warning about the virilizing effect on a male or
h, s4 H1 ?' ^. O0 Tfemale child who might come in contact with some-
# [& x' W; I5 g0 vone using any of these products.( V. A% Z$ o' j9 q
References# g; e; G0 h9 f2 R% \; w5 t
1. Styne DM. The testes: disorder of sexual differentiation
& W0 W1 z1 T) q3 k% rand puberty in the male. In: Sperling MA, ed. Pediatric
- p2 z3 f9 l- p, T+ gEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
7 d7 {8 T K7 v2002: 565-628.6 Y4 T) J/ n+ H, {+ i
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
- D/ g3 s/ H1 V, apuberty in children with tumours of the suprasellar pineal |
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