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Sexual Precocity in a 16-Month-Old
0 L. S4 N7 h' z) v& vBoy Induced by Indirect Topical* @. | P6 T1 p& i9 A! w9 s
Exposure to Testosterone0 T" u2 T, o( J/ q& e: [1 X# K
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2, b, P. P* R. C6 \2 s. Q
and Kenneth R. Rettig, MD10 p7 I9 O& Q3 j% @/ L* R, q
Clinical Pediatrics
W$ g& [* j1 ?8 L8 U4 QVolume 46 Number 6! y; e2 ], b; i% ~% @0 c) H' A
July 2007 540-543
% P0 d; r7 L( C: u9 B© 2007 Sage Publications
5 {& [: F$ ^6 f0 A# C. Y- L8 F10.1177/0009922806296651
# M* _9 X! _. z6 Jhttp://clp.sagepub.com' P) ~7 S" k, B+ K
hosted at& g7 o3 W2 U# V; W0 r7 E5 H1 F
http://online.sagepub.com
% f+ a% C5 d/ N5 B3 T& Z0 N1 tPrecocious puberty in boys, central or peripheral,
3 ^ x4 n, h" }4 `6 C# O& bis a significant concern for physicians. Central
* i! L& s+ _$ ~6 Eprecocious puberty (CPP), which is mediated3 V3 v( w t- L0 s, Y: f4 I& y1 ~
through the hypothalamic pituitary gonadal axis, has4 B! g Q9 g& c( R ^: G
a higher incidence of organic central nervous system
T) {3 ]3 E1 @. \lesions in boys.1,2 Virilization in boys, as manifested
1 F% k: c( n, F2 u9 A% {/ Yby enlargement of the penis, development of pubic% r" M7 y& u% V
hair, and facial acne without enlargement of testi-
2 ?$ b/ G" P- z/ ^3 Vcles, suggests peripheral or pseudopuberty.1-3 We3 f* ? d; W g( L0 Y
report a 16-month-old boy who presented with the. T3 H8 ~/ N% A% p' R* a
enlargement of the phallus and pubic hair develop-4 r9 a8 P9 s& h! y* G
ment without testicular enlargement, which was due3 w( j x; F. e+ l
to the unintentional exposure to androgen gel used by
! e `+ T$ m+ F: v6 U E4 @the father. The family initially concealed this infor-" b, S* g( P2 ]
mation, resulting in an extensive work-up for this }* y3 n% f+ c, \% _/ i; _
child. Given the widespread and easy availability of
- }! o# V i% A7 ~, y ]9 ctestosterone gel and cream, we believe this is proba-
% |5 g6 q, Z5 ^* _, Hbly more common than the rare case report in the/ @5 c% K x: }0 y* Y2 W# g
literature.4" g a& X/ x5 c$ n7 v% `
Patient Report2 `# J! R1 g' W |$ O$ g
A 16-month-old white child was referred to the6 q# B7 i9 X! N$ K a/ J6 r
endocrine clinic by his pediatrician with the concern0 V, m7 v3 g G6 O
of early sexual development. His mother noticed. Z3 _+ y" y$ q+ o# m9 t
light colored pubic hair development when he was" }2 `+ e! h/ D! l5 \) P0 F
From the 1Division of Pediatric Endocrinology, 2University of
( m7 u8 O( u5 _, U- ?South Alabama Medical Center, Mobile, Alabama.
9 a* `1 B/ q8 @7 W9 `1 L0 ^Address correspondence to: Samar K. Bhowmick, MD, FACE,
6 C1 @: y1 h3 c0 y* R* NProfessor of Pediatrics, University of South Alabama, College of
9 J+ P8 m+ m1 R5 d- LMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
$ F7 F5 ]% H B5 o/ }8 I1 ?* \e-mail: [email protected].0 i- p: f5 ?, k
about 6 to 7 months old, which progressively became
) ?: B; p" ], i$ {darker. She was also concerned about the enlarge-
+ N! }; r/ z+ N9 Xment of his penis and frequent erections. The child' } B' x; e* O
was the product of a full-term normal delivery, with y3 T8 r- \4 P2 ^, G# v' m
a birth weight of 7 lb 14 oz, and birth length of
2 z+ o9 _ n* Y1 V, ?: o: J20 inches. He was breast-fed throughout the first year
: g p9 }# N9 t N3 `of life and was still receiving breast milk along with
& x' L0 P! i4 a! y& @solid food. He had no hospitalizations or surgery,/ E0 \# z, Q. m e3 k8 W5 I, a2 D
and his psychosocial and psychomotor development, P# ?# q4 o% [
was age appropriate.
+ I& [4 a$ P, v* S5 ~* B7 TThe family history was remarkable for the father,
6 R/ f) f D: A8 l3 lwho was diagnosed with hypothyroidism at age 16,
- e( S, ]% w+ b3 Ewhich was treated with thyroxine. The father’s
4 z, J! M) f+ k( Q6 M$ q% A* y$ pheight was 6 feet, and he went through a somewhat5 j& h! D' I+ ^3 j% u" Z
early puberty and had stopped growing by age 14.
( L7 {5 i$ p/ ~" ?1 H7 `, HThe father denied taking any other medication. The% H' H* M4 M5 h. N
child’s mother was in good health. Her menarche0 O+ |8 s! F+ H- S3 x3 a
was at 11 years of age, and her height was at 5 feet
2 {: @# M3 m5 {& y( ]* Q, w5 inches. There was no other family history of pre-7 M2 o, t0 H0 B2 i: M+ [
cocious sexual development in the first-degree rela-
1 t* m% D+ t3 j% Utives. There were no siblings.2 v& x: w: ~" u) u% B
Physical Examination
* {9 Z3 _# A q9 ~6 F/ i7 gThe physical examination revealed a very active,
7 Y- ^' i: g3 Q0 p# Dplayful, and healthy boy. The vital signs documented& X* i/ z! w4 J0 X4 z
a blood pressure of 85/50 mm Hg, his length was
2 m; |# j! W- Y c90 cm (>97th percentile), and his weight was 14.4 kg8 Y/ Z5 k& r1 s5 C8 {) n- _. D5 W' O
(also >97th percentile). The observed yearly growth
) j, W3 s9 _- S2 Lvelocity was 30 cm (12 inches). The examination of+ N' d. q z8 A
the neck revealed no thyroid enlargement.
9 U6 \' `: H7 S1 e- KThe genitourinary examination was remarkable for
2 M5 P/ R j3 N+ ` R9 B Wenlargement of the penis, with a stretched length of* W& E1 Z! C2 p& k& E3 b3 n
8 cm and a width of 2 cm. The glans penis was very well+ N3 o. P2 ^' T
developed. The pubic hair was Tanner II, mostly around% v% T. E6 f3 \
540
5 ?+ A& ^2 E+ U: ~" t @* yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
8 b. w; @1 k8 _+ M; [9 }4 [the base of the phallus and was dark and curled. The
* V" j" m- I8 u3 e- E6 _4 Ttesticular volume was prepubertal at 2 mL each.
4 D. |/ |; W `! Q! O- MThe skin was moist and smooth and somewhat! S) u2 o8 C e5 S
oily. No axillary hair was noted. There were no' X; N+ p# G: {0 N: j
abnormal skin pigmentations or café-au-lait spots.+ w0 Y, W9 G3 H) u% h1 H# f& N
Neurologic evaluation showed deep tendon reflex 2+7 l6 \, u- O3 }3 }
bilateral and symmetrical. There was no suggestion
) X4 v/ Q. b9 T5 ]6 h+ x% j- t8 Xof papilledema.
3 }- u# G w/ j+ lLaboratory Evaluation
: V: o6 m R! i3 [; A \$ DThe bone age was consistent with 28 months by# G" a: l1 e" O! W" a
using the standard of Greulich and Pyle at a chrono-
) \- g" R) A' Z' s- Mlogic age of 16 months (advanced).5 Chromosomal
3 b3 o( K: f+ }7 s: X6 u Gkaryotype was 46XY. The thyroid function test
# v4 Z# I" W3 M# ^5 Z( Vshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
# [ R2 C6 W" y$ V9 `lating hormone level was 1.3 µIU/mL (both normal).
$ _# N3 ?6 h! K) r5 Y6 k' IThe concentrations of serum electrolytes, blood
! u; _3 U1 I& S l# \: q/ F1 k( Yurea nitrogen, creatinine, and calcium all were# f; K: k7 b$ a
within normal range for his age. The concentration2 i1 K, `% [, m4 P4 q5 X3 j, q
of serum 17-hydroxyprogesterone was 16 ng/dL9 _2 ~- m7 A, ?+ }5 J
(normal, 3 to 90 ng/dL), androstenedione was 204 l) g7 k& x+ M" [+ }% l
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
0 J) W* e3 S, |# S. `. U/ _" Uterone was 38 ng/dL (normal, 50 to 760 ng/dL), R3 e, @, [2 d
desoxycorticosterone was 4.3 ng/dL (normal, 7 to; U6 I. v6 H4 h
49ng/dL), 11-desoxycortisol (specific compound S)
' m% c$ r" L, q- r* L$ Cwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
* C" d: p8 h! T, ] Itisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
5 y: O, T; A! J# I! Ytestosterone was 60 ng/dL (normal <3 to 10 ng/dL),3 X: K: H" y' n- }6 F
and β-human chorionic gonadotropin was less than; ~% m! I5 {$ `; m
5 mIU/mL (normal <5 mIU/mL). Serum follicular
9 f0 T$ V3 N" qstimulating hormone and leuteinizing hormone! N' J# W; |; Y4 U6 h# R
concentrations were less than 0.05 mIU/mL
8 M3 U1 j) q8 M1 R; H8 k(prepubertal).8 c0 G* W; U8 Q# b* T! [
The parents were notified about the laboratory+ f4 s! K& B- \5 W k3 X3 G0 y# B7 L
results and were informed that all of the tests were
+ J, m2 M3 L5 [4 knormal except the testosterone level was high. The
- ^; l9 ]3 y6 u: i" qfollow-up visit was arranged within a few weeks to
$ N$ I5 y Y! K$ uobtain testicular and abdominal sonograms; how-9 b U+ `& L1 y; b e+ z
ever, the family did not return for 4 months.+ w# G7 Q0 w6 O- K5 f8 \% s
Physical examination at this time revealed that the8 j# j' g# x* |- L7 B
child had grown 2.5 cm in 4 months and had gained
# k2 y! |/ U8 \ F: p/ w7 I6 [2 kg of weight. Physical examination remained. _& `4 I, M$ h- t: Z/ x- }
unchanged. Surprisingly, the pubic hair almost com-2 j% v& ]; T3 b
pletely disappeared except for a few vellous hairs at
5 x2 O3 | M1 [% C& `1 f& x# M5 {the base of the phallus. Testicular volume was still 2
1 [' ^; N+ ?' ?2 t7 w% ]% GmL, and the size of the penis remained unchanged.3 s# E8 G( h, Y
The mother also said that the boy was no longer hav-
4 H. ^# S* O" I+ T8 ning frequent erections.
. F' X" C8 t7 I5 s/ C" d- F! d5 VBoth parents were again questioned about use of" x7 y3 \3 Y5 w, _3 J8 s
any ointment/creams that they may have applied to$ a- }* |0 U% c, x2 r
the child’s skin. This time the father admitted the- S ?6 q/ x0 k7 t
Topical Testosterone Exposure / Bhowmick et al 5419 x2 w2 [ U; r0 \; n4 q: J
use of testosterone gel twice daily that he was apply-" r+ _5 y; l; ]5 W( R) n6 D
ing over his own shoulders, chest, and back area for# ^6 R, D) f1 U) s( r$ C
a year. The father also revealed he was embarrassed
: I5 r- O6 Q' [0 Kto disclose that he was using a testosterone gel pre-, V" |8 f: h9 v% k$ Y7 W
scribed by his family physician for decreased libido
7 d) h, ?9 y, I M. h5 F0 esecondary to depression.
3 k' _4 V1 P0 JThe child slept in the same bed with parents.
4 @# S" y5 D, } M" g0 W* QThe father would hug the baby and hold him on his7 ^' B0 h8 ` i3 l
chest for a considerable period of time, causing sig-
( S9 I4 y' L, Lnificant bare skin contact between baby and father.
. _$ P% d0 n0 c$ bThe father also admitted that after the phone call,
( ]( j: V: {2 {2 A8 w3 T1 v+ d9 `when he learned the testosterone level in the baby
8 e- W$ ?- {, z& ?) W/ c5 {1 {was high, he then read the product information
, r' g9 c+ a9 F# C4 p2 Z( b' R# apacket and concluded that it was most likely the rea-
3 W4 F! {5 B- \6 T$ R' Y; r3 tson for the child’s virilization. At that time, they
1 N0 ?) `2 V- M% l' n* u0 P- m0 `decided to put the baby in a separate bed, and the+ D B5 j* t( w$ G
father was not hugging him with bare skin and had
0 `9 b7 O0 Y- w2 { }been using protective clothing. A repeat testosterone0 R* R" ]+ s. }0 m+ ]
test was ordered, but the family did not go to the6 O2 _. R" `! e' S' b
laboratory to obtain the test.
; ~; h/ U0 @: }0 B# l ~Discussion9 w: v) V) x, I3 F I% f6 O! @
Precocious puberty in boys is defined as secondary
, d# _) {# {; B/ ?sexual development before 9 years of age.1,4& `. b4 y: S9 M8 r: X( x P8 @
Precocious puberty is termed as central (true) when" v N# F' x. f
it is caused by the premature activation of hypo-
" j8 m4 y1 S2 w% G2 C& z+ Pthalamic pituitary gonadal axis. CPP is more com-2 P7 n: ?0 _ q1 m0 @2 ?) }
mon in girls than in boys.1,3 Most boys with CPP, G7 E' M4 A$ D6 k, n X
may have a central nervous system lesion that is; b1 G+ y. H4 U) X* B
responsible for the early activation of the hypothal-/ |+ e. s' {$ S/ q( ?0 k
amic pituitary gonadal axis.1-3 Thus, greater empha-1 H9 y6 X1 V/ \! @' G( |1 R7 @* f
sis has been given to neuroradiologic imaging in
7 k$ J! d' N0 e' Vboys with precocious puberty. In addition to viril-
! W4 D# C" q/ Q; Q: k) n# }8 I8 Q" Rization, the clinical hallmark of CPP is the symmet-
+ D$ `8 ?* E4 Y1 trical testicular growth secondary to stimulation by! r! {9 @5 x+ Z: q& G3 a e$ o3 f, a
gonadotropins.1,3
7 |/ h1 z) L) cGonadotropin-independent peripheral preco-/ `& I& o; l a7 J5 x
cious puberty in boys also results from inappropriate# m" n; Z( |) Q/ s1 K+ }% K3 |+ c
androgenic stimulation from either endogenous or
* l& O7 @+ L! c/ s8 G3 \0 Dexogenous sources, nonpituitary gonadotropin stim-
/ y8 o) h5 f4 X7 J; Qulation, and rare activating mutations.3 Virilizing! O; e1 ?/ d: u5 X; g, {) k) {
congenital adrenal hyperplasia producing excessive) m5 r. x0 S/ g* L
adrenal androgens is a common cause of precocious
5 E! p, y2 e8 c* `0 Opuberty in boys.3,4
9 Y+ M" j& N oThe most common form of congenital adrenal
: ]' @& H/ _# X3 {hyperplasia is the 21-hydroxylase enzyme deficiency.
3 k$ [4 _4 U1 @' G3 C; cThe 11-β hydroxylase deficiency may also result in
4 c: e( [- \* H2 ^) {; r5 x' b# ~excessive adrenal androgen production, and rarely,2 m8 S( h/ |: l( a
an adrenal tumor may also cause adrenal androgen
) N# Q7 z7 y& cexcess.1,3
8 @, D! c& f5 ]+ K9 F; f6 k+ pat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
$ q0 M! S7 Q, R6 q542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
7 ?3 R+ {- f( m' g7 V4 {- J% nA unique entity of male-limited gonadotropin-
+ |5 @ u! t! l" _! [3 y( uindependent precocious puberty, which is also known
- [: D. A: L# W0 R4 Sas testotoxicosis, may cause precocious puberty at a6 p' J& k/ I. @& Z- W V& Q; D
very young age. The physical findings in these boys7 B/ Q' Y8 G( p, D
with this disorder are full pubertal development,
9 I, x. P5 s) Dincluding bilateral testicular growth, similar to boys
3 u: Q0 j" o% B" }) z+ p6 xwith CPP. The gonadotropin levels in this disorder
6 ?; C+ M' b4 t4 care suppressed to prepubertal levels and do not show
4 F1 X+ f1 d) x3 {: D0 Wpubertal response of gonadotropin after gonadotropin-3 U* w! F, h' U/ X
releasing hormone stimulation. This is a sex-linked# ?1 p! |: ~4 S6 W5 w
autosomal dominant disorder that affects only
% R1 f" z$ R& `- ^" f! }males; therefore, other male members of the family( W$ d" @! T0 M" i% q, [/ `: p+ e
may have similar precocious puberty.3
2 U$ z+ T" ?" EIn our patient, physical examination was incon-
2 M/ E5 o* X, \) q; H/ Ssistent with true precocious puberty since his testi-
2 U9 H8 F7 [; j5 Q4 {0 D! j/ Qcles were prepubertal in size. However, testotoxicosis
9 `: p2 ?7 V4 M. W" Fwas in the differential diagnosis because his father4 m( Z7 ^* t7 m4 M; s
started puberty somewhat early, and occasionally,. ^3 z( Z, Z! k6 G8 Z# F
testicular enlargement is not that evident in the9 e7 a3 }7 H; S8 W5 I3 @9 d. {
beginning of this process.1 In the absence of a neg-3 b6 `. p. y3 h3 F$ V" U" A7 d# v7 g
ative initial history of androgen exposure, our, J0 z$ X0 u$ Z( ^# G1 _" x
biggest concern was virilizing adrenal hyperplasia,$ y0 _ j! J/ E
either 21-hydroxylase deficiency or 11-β hydroxylase
1 a7 X( C# x9 ~) [2 D: |deficiency. Those diagnoses were excluded by find-8 c* D- ] D5 O" g3 _
ing the normal level of adrenal steroids.. C3 M6 |9 A2 F0 b
The diagnosis of exogenous androgens was strongly( `2 N8 d& r% D! U- E
suspected in a follow-up visit after 4 months because" n1 S/ C, v- E9 I* P& O7 M
the physical examination revealed the complete disap-2 ~4 q$ c y6 G! m- ~
pearance of pubic hair, normal growth velocity, and
% l' [/ Y' {* n: Ndecreased erections. The father admitted using a testos-
6 B% v* H; h4 g% s. D- Uterone gel, which he concealed at first visit. He was
1 `3 U5 J O8 H* _% Cusing it rather frequently, twice a day. The Physicians’( J D" h% V. j0 D1 `4 m- p
Desk Reference, or package insert of this product, gel or
@+ ]3 V4 G9 [/ |! y( O8 Acream, cautions about dermal testosterone transfer to* K% h% _. T2 n. C, o, i
unprotected females through direct skin exposure.
. E! o! W1 e: X( zSerum testosterone level was found to be 2 times the
$ z9 U6 Z; q* S. m+ E; [2 Sbaseline value in those females who were exposed to0 C+ }1 A$ x& Y3 m9 A+ w0 h2 l
even 15 minutes of direct skin contact with their male
( k1 s4 j; z5 b: \) b. Bpartners.6 However, when a shirt covered the applica-
8 L, X& s0 g5 Otion site, this testosterone transfer was prevented.
( [) V3 h8 y, i9 e$ ~: l% V6 X$ I! UOur patient’s testosterone level was 60 ng/mL,( z+ L% D) E& A1 \" W
which was clearly high. Some studies suggest that1 Z2 p* z- q" z1 R8 T+ a
dermal conversion of testosterone to dihydrotestos-* y3 H; H2 o5 j: I; Z* ]
terone, which is a more potent metabolite, is more
0 X: T& f9 s" N# jactive in young children exposed to testosterone
, ]$ S3 @: m( t. `exogenously7; however, we did not measure a dihy-3 x, X- N i. r8 [
drotestosterone level in our patient. In addition to
6 V# v* i5 o* K" k; N( Hvirilization, exposure to exogenous testosterone in
9 W* |% t5 ]4 P# {3 a1 V: [children results in an increase in growth velocity and
, m5 f2 B/ y& V; ]3 F: u+ }advanced bone age, as seen in our patient.
/ E7 L5 V- e. ?# u& u( n1 T f2 PThe long-term effect of androgen exposure during
- H A. m" ^; I( h6 V( J" Nearly childhood on pubertal development and final
8 D) S" K6 X- U% O5 Nadult height are not fully known and always remain
0 d1 _' C$ O1 B( G; g$ Ja concern. Children treated with short-term testos-
+ j+ D2 { t6 Jterone injection or topical androgen may exhibit some
5 A' r* X9 @4 ~5 ]9 g* x; a* n% oacceleration of the skeletal maturation; however, after
; f/ ]: | A# K9 e. c" K5 W2 V, lcessation of treatment, the rate of bone maturation
6 K" G! }4 n# O# Bdecelerates and gradually returns to normal.8,9! M: s5 b& L" W) Q8 v, f
There are conflicting reports and controversy1 v) c7 V3 g' l2 `9 u
over the effect of early androgen exposure on adult
) D" a0 k; d6 x- h+ upenile length.10,11 Some reports suggest subnormal" O1 x; m- k% [3 ]
adult penile length, apparently because of downreg-: n. Y( _9 g! \2 p8 l& y
ulation of androgen receptor number.10,12 However,
6 _$ Q) s. X0 ~+ C" X3 B/ uSutherland et al13 did not find a correlation between
{2 V+ m2 M6 g1 T1 A( }* Q# R H6 Zchildhood testosterone exposure and reduced adult8 ~+ q: L' B' z
penile length in clinical studies.
4 h% ?& G% u& V+ QNonetheless, we do not believe our patient is2 k) i# m5 l \6 e% I0 o
going to experience any of the untoward effects from
! F8 c s: Z/ k/ h' Z5 Mtestosterone exposure as mentioned earlier because
1 C9 C" D+ a. ]the exposure was not for a prolonged period of time.
6 e& G4 K, w* Q' h9 X3 C7 ~Although the bone age was advanced at the time of
& {0 Q0 ?3 n6 z% Cdiagnosis, the child had a normal growth velocity at
# A. G7 P8 x9 N4 b* R" @9 j) Bthe follow-up visit. It is hoped that his final adult( N) u% u8 J8 F2 Z
height will not be affected.
5 C' S n Y. `" |Although rarely reported, the widespread avail-9 M6 N4 Q! ~9 i5 S0 Y: B, d/ Q
ability of androgen products in our society may# |4 {+ u i. [; o7 X$ a
indeed cause more virilization in male or female
: A7 `9 ^1 J$ I1 v1 uchildren than one would realize. Exposure to andro-
5 h5 S- D9 j+ ]. v$ bgen products must be considered and specific ques-% F8 k1 R% \7 x% K& { ~! t
tioning about the use of a testosterone product or
& t: c. |+ D; O& c& dgel should be asked of the family members during
- o/ }: W% l* R4 e7 Q7 {the evaluation of any children who present with vir-( T& I7 r# E* s; E4 @: M
ilization or peripheral precocious puberty. The diag-
, d# c9 T1 `) J( znosis can be established by just a few tests and by* V& D$ E+ ]2 w% {2 e7 H( U! O2 k
appropriate history. The inability to obtain such a
" Y+ v) P0 X# `& Thistory, or failure to ask the specific questions, may
" H9 n1 R) s/ Q6 O- n$ Gresult in extensive, unnecessary, and expensive
4 \! X, `/ a% Q8 |7 Yinvestigation. The primary care physician should be
+ [) Z1 H* ?1 U. u9 zaware of this fact, because most of these children
8 j8 p; V1 |8 U3 Cmay initially present in their practice. The Physicians’
' D* k* |7 s$ I' a" r* h& ~Desk Reference and package insert should also put a: z# ~3 a) S2 c. [: M
warning about the virilizing effect on a male or
2 m0 s( Z, q' D' e' Q/ H6 ?( Cfemale child who might come in contact with some-
( `/ U9 k: v8 F( @one using any of these products.; z$ V& j4 W3 w* }* E- I
References
) w. j' Z9 }5 X* j3 F1. Styne DM. The testes: disorder of sexual differentiation* h J6 R& t0 M/ f$ A* a
and puberty in the male. In: Sperling MA, ed. Pediatric0 w% `; } q- n9 |6 A
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;9 T5 v* A4 M) F/ @* B0 V- p
2002: 565-628.
1 p+ Q& S$ q8 b3 }' o3 ?1 D2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious/ m0 D+ C, A8 S' b7 V9 N9 o9 v
puberty in children with tumours of the suprasellar pineal |
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