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Sexual Precocity in a 16-Month-Old
6 }8 S5 A0 o2 N7 F, v0 dBoy Induced by Indirect Topical
& @6 X) ]: Q2 c# n* R fExposure to Testosterone" |' {& S9 y9 e4 X: j) f/ z
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
; b* b% o( v3 G7 f) e) R1 pand Kenneth R. Rettig, MD1
3 r( H( c7 q3 [" P! NClinical Pediatrics
- G$ ?- J# T4 fVolume 46 Number 64 J7 g/ u; u G
July 2007 540-5435 J# Y( U3 z' L1 O4 u" Z, A
© 2007 Sage Publications
% M) G V% u0 k, Q6 x8 s! t" Q' Y10.1177/0009922806296651
) P8 x! m, ~$ f% Y! Vhttp://clp.sagepub.com
! p6 N1 @" w h7 mhosted at
, F: N. \0 A4 d6 q ^http://online.sagepub.com
7 H1 d: ?! ?5 z6 W; {) Q kPrecocious puberty in boys, central or peripheral,) [8 g' L' c$ X: `. D! L7 i7 \! ?
is a significant concern for physicians. Central
$ g/ X* Z. {( k8 [6 sprecocious puberty (CPP), which is mediated
5 x7 ]# ^, k) ythrough the hypothalamic pituitary gonadal axis, has1 T* Q" s4 j2 T2 P7 o
a higher incidence of organic central nervous system
$ [/ Y* }$ v. K! nlesions in boys.1,2 Virilization in boys, as manifested
( }2 E0 F* N* y2 x& Mby enlargement of the penis, development of pubic% W2 p; {! h3 z! n! B) r3 t
hair, and facial acne without enlargement of testi-. K# g' m+ l& ^, ^. u
cles, suggests peripheral or pseudopuberty.1-3 We' s. y3 v( [- S. h3 K8 [0 ]
report a 16-month-old boy who presented with the
- J. N, D# T6 z, Y! p7 ?) @4 Z- Henlargement of the phallus and pubic hair develop-
" V. e0 J4 |9 P, j' z9 k# Kment without testicular enlargement, which was due
! I1 s8 H9 x- @+ `4 v! eto the unintentional exposure to androgen gel used by- S; K9 e$ R" D2 ?& Q
the father. The family initially concealed this infor-. |+ G6 a+ s1 v4 e+ B
mation, resulting in an extensive work-up for this
8 r" N. H9 o! {3 T7 a" N3 Echild. Given the widespread and easy availability of C- _( H9 ~6 U$ `1 P) c5 D
testosterone gel and cream, we believe this is proba-2 ]- d6 Q* c1 i/ c
bly more common than the rare case report in the. m! d0 G% e- g+ P
literature.48 t9 o; k8 q3 r
Patient Report1 }9 r/ y9 h8 e( j
A 16-month-old white child was referred to the: B+ s8 ?: b, Y2 ]8 n# _
endocrine clinic by his pediatrician with the concern( Q1 H8 D0 G" t* W8 Y" |
of early sexual development. His mother noticed
# q: H+ A% N U- B4 A% Mlight colored pubic hair development when he was
% j9 F1 y7 J/ Y+ C5 \+ Q: c0 k3 fFrom the 1Division of Pediatric Endocrinology, 2University of
6 J3 d! o# Y* X( d) }5 D, @+ b8 V( sSouth Alabama Medical Center, Mobile, Alabama.1 | M, f! h& C. Z* f; R
Address correspondence to: Samar K. Bhowmick, MD, FACE,
! U; {, J4 Q4 w! U# K" ^1 ZProfessor of Pediatrics, University of South Alabama, College of4 I2 B! c# ]6 n, ~
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
8 d9 M: T. s) Fe-mail: [email protected].
) G4 V/ n& ?9 V8 C: l) qabout 6 to 7 months old, which progressively became" |, R6 @0 I/ v/ Y* Y. Q
darker. She was also concerned about the enlarge-" K7 z+ W$ ?: | c% Z
ment of his penis and frequent erections. The child
4 t8 p+ t7 K& E4 Hwas the product of a full-term normal delivery, with
; h8 m* V/ y, Ja birth weight of 7 lb 14 oz, and birth length of: ~ I! U, \' M* w
20 inches. He was breast-fed throughout the first year4 }+ o X8 {* f" c
of life and was still receiving breast milk along with
. k9 h1 v- C$ d2 R+ |+ Fsolid food. He had no hospitalizations or surgery,3 I9 O" @8 `& f' p( E% q% R; b: m" l' L
and his psychosocial and psychomotor development
; V1 s8 g% @* t1 m& S: @was age appropriate.
2 S8 v2 t! O7 sThe family history was remarkable for the father,
9 q0 Y! T3 }4 ~- ^8 X& o+ a4 ywho was diagnosed with hypothyroidism at age 16,( {0 w9 O( D `; P
which was treated with thyroxine. The father’s" _3 w$ v8 t6 ~1 f
height was 6 feet, and he went through a somewhat
5 F, S& ~2 j, F. H* `early puberty and had stopped growing by age 14.4 |+ t& s+ ]! T/ N" P# b
The father denied taking any other medication. The) n3 C2 X( `; R1 h
child’s mother was in good health. Her menarche
9 Q7 `: y+ H, D$ ?- \# A2 {was at 11 years of age, and her height was at 5 feet( ^! x! z1 {$ I' F0 X
5 inches. There was no other family history of pre-
3 [* E4 d _6 n. |$ s4 L6 e5 y. mcocious sexual development in the first-degree rela-
0 X k& W( M$ ftives. There were no siblings.$ o" Q, u C$ ^3 m
Physical Examination
; v {( o1 D5 M, L# e9 S% e7 Y' mThe physical examination revealed a very active,8 y$ ^; i' o" A; L) c! W" |1 i/ @* l
playful, and healthy boy. The vital signs documented" h% _( o; G$ m, B
a blood pressure of 85/50 mm Hg, his length was
4 ~4 b' ]3 S1 S8 Y+ f90 cm (>97th percentile), and his weight was 14.4 kg |" Y" ] e7 ^" ~/ ~4 z( J
(also >97th percentile). The observed yearly growth
3 k% c0 o5 S. Avelocity was 30 cm (12 inches). The examination of
2 G! z$ \( I! R# F3 H- y! ^the neck revealed no thyroid enlargement.1 e; C# U+ U$ m2 C- s$ h
The genitourinary examination was remarkable for2 Y2 K0 g. e& p2 Q+ U* N
enlargement of the penis, with a stretched length of3 P* E+ @, m7 y) m4 u! f) s
8 cm and a width of 2 cm. The glans penis was very well) Q9 W# }! l( Q& p2 V& g \
developed. The pubic hair was Tanner II, mostly around1 v. y- m+ ^. B5 I8 V5 c
540" O6 F) `0 W% B' O# I9 y
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
0 E" b: O! y' }the base of the phallus and was dark and curled. The% } x6 P5 k9 J% M2 ^- I# @, G- _
testicular volume was prepubertal at 2 mL each.
! q) i1 o! S* bThe skin was moist and smooth and somewhat+ [' p, H* O: p& s
oily. No axillary hair was noted. There were no% @! L6 P( j& |4 x5 Y$ w; {# o
abnormal skin pigmentations or café-au-lait spots.
# S7 Z. I) t8 f' D# }Neurologic evaluation showed deep tendon reflex 2+. O% I, t1 Y6 q- l4 c9 U/ t
bilateral and symmetrical. There was no suggestion) [. P- i, O/ K0 K: M) q0 ^9 j
of papilledema.
9 @ i: L7 n- ` L5 r/ @Laboratory Evaluation
. e! U- L& _- G% {The bone age was consistent with 28 months by
, L& P( N& n* E0 musing the standard of Greulich and Pyle at a chrono-
`: Y( P7 f# V/ o! [logic age of 16 months (advanced).5 Chromosomal
, e+ p6 p5 K' Z; Q7 f) ^2 l& w1 J" ]karyotype was 46XY. The thyroid function test3 d" u0 x V5 E% d1 F! h! h
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
6 Q" {& e% N+ o. L2 }; klating hormone level was 1.3 µIU/mL (both normal).
6 D3 ~- O( M; n& Y# xThe concentrations of serum electrolytes, blood
8 j- ?# [ c( i9 G' ?7 K6 O: i* j- o1 Vurea nitrogen, creatinine, and calcium all were
6 a) e+ K# O, m: Pwithin normal range for his age. The concentration2 Q: x4 A9 n' F- K
of serum 17-hydroxyprogesterone was 16 ng/dL
$ s2 j3 a, g9 k, Z; H! E(normal, 3 to 90 ng/dL), androstenedione was 206 I+ U% l f k8 }4 B9 @
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
3 z; v$ \5 z% F- v& Sterone was 38 ng/dL (normal, 50 to 760 ng/dL),
% |" o4 ^) R6 \% sdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
4 y0 b0 F6 L8 v49ng/dL), 11-desoxycortisol (specific compound S)1 ?# H7 q; I, s+ o3 c. G
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
, p7 ~' ]* M- t" ttisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total+ S4 A# H% Y0 W( s: ]; R( [1 N
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),) k! b- k7 r4 S& E1 Y5 c
and β-human chorionic gonadotropin was less than0 V7 L: |3 ^+ t. j8 M; C
5 mIU/mL (normal <5 mIU/mL). Serum follicular
5 ]4 ~' J8 O2 Q g9 Lstimulating hormone and leuteinizing hormone
; B( U" I' ]: Rconcentrations were less than 0.05 mIU/mL U) ?+ M1 m) f+ D k8 G
(prepubertal).: `- x6 x) F1 z$ F# o# l
The parents were notified about the laboratory* Y$ b- Q' O) \. c8 f8 \9 o6 L
results and were informed that all of the tests were
2 t% ]/ Q- }# b4 _! v( X; Bnormal except the testosterone level was high. The( T3 s' K6 U B% E
follow-up visit was arranged within a few weeks to0 v3 X9 ~# ^ Q% n; A, F3 g
obtain testicular and abdominal sonograms; how-
" A1 `2 N. j. x/ R( J- A! Lever, the family did not return for 4 months.
. n# o, }. X' y) JPhysical examination at this time revealed that the
1 e1 W% B7 o& k: @1 Q% p% @child had grown 2.5 cm in 4 months and had gained* g: r+ G: T; {9 g K0 S* ]- `( }& @
2 kg of weight. Physical examination remained8 ^0 [5 k+ K0 S9 P1 M1 n
unchanged. Surprisingly, the pubic hair almost com-: ~9 G* ^# q) l
pletely disappeared except for a few vellous hairs at
9 ^, M' }9 k& O9 _5 ~the base of the phallus. Testicular volume was still 2+ U: Y# m% P7 |0 g1 l
mL, and the size of the penis remained unchanged.0 r% R; i" b" G$ @7 ^7 j: K/ C
The mother also said that the boy was no longer hav-- F% z5 k) [, T# z( p
ing frequent erections.
" C7 y2 A3 h8 R8 pBoth parents were again questioned about use of
: M ^: L6 ]& ~' g3 B! a+ @any ointment/creams that they may have applied to
- L) K+ Y i' a: m7 a9 K: bthe child’s skin. This time the father admitted the
0 O+ U" v1 a! YTopical Testosterone Exposure / Bhowmick et al 541
; a9 j1 j* t. E, R% s3 c* {use of testosterone gel twice daily that he was apply-
3 b6 x; n" o v e' q( Eing over his own shoulders, chest, and back area for
4 ^0 t1 x. s4 G8 U+ ]2 Y7 Qa year. The father also revealed he was embarrassed
* X$ m0 U1 X+ b+ `2 xto disclose that he was using a testosterone gel pre-: L" N+ }& l7 J* L3 L) q
scribed by his family physician for decreased libido# s; P; w- r2 } S9 C+ ^3 R
secondary to depression.
1 ]7 c- K8 d% CThe child slept in the same bed with parents.
* Y' @0 N! O2 J0 \( T- EThe father would hug the baby and hold him on his) c/ p3 B/ U6 s
chest for a considerable period of time, causing sig-8 [8 t1 o' ^! S5 v& n# F" @
nificant bare skin contact between baby and father.
( l5 x4 O" E. B: P+ R, T8 MThe father also admitted that after the phone call,
& o& I4 X, n7 k+ u9 U8 vwhen he learned the testosterone level in the baby
& H% ?) ^' o' D# P. F6 Swas high, he then read the product information3 J# R. b# B# V' i4 l
packet and concluded that it was most likely the rea-% v- E" @3 A" \
son for the child’s virilization. At that time, they
$ G& ]# r. V" _# Fdecided to put the baby in a separate bed, and the
j2 `: `6 |" d( s7 |4 Cfather was not hugging him with bare skin and had: `' v4 m" S) W$ U
been using protective clothing. A repeat testosterone
1 J8 a" x. f& x) q$ p& m8 ftest was ordered, but the family did not go to the& b; U6 l6 J4 w0 k; M0 \
laboratory to obtain the test.
8 B! |7 B1 X( s8 c3 K5 g* jDiscussion
5 F+ a$ }/ T- U; Y" Q2 H2 v- xPrecocious puberty in boys is defined as secondary
: [: k7 ?( c, Dsexual development before 9 years of age.1,41 C( Z* k: F1 F
Precocious puberty is termed as central (true) when; c0 g7 e0 i8 r/ y% @
it is caused by the premature activation of hypo-5 w* `+ |# [5 L5 V& J' K8 }- m
thalamic pituitary gonadal axis. CPP is more com-
" {( e) {8 L3 Z3 Umon in girls than in boys.1,3 Most boys with CPP
' e6 [4 k% W: b( n- A" x2 L1 I7 fmay have a central nervous system lesion that is3 n0 ^. g8 C5 j0 r+ m6 W
responsible for the early activation of the hypothal-
5 |. i' V0 I* f. a5 z, e+ q( L& @amic pituitary gonadal axis.1-3 Thus, greater empha-
" t2 i d6 Q7 D9 ssis has been given to neuroradiologic imaging in8 z- P0 ~: R( {9 A% `
boys with precocious puberty. In addition to viril-+ g; v. H, r& G- ?
ization, the clinical hallmark of CPP is the symmet-: c* d- L. B+ B) `* {: U$ s# B7 d
rical testicular growth secondary to stimulation by- P( }/ w9 F6 _" ^8 J. ^
gonadotropins.1,3
! V3 H9 k, C. j8 g0 VGonadotropin-independent peripheral preco-3 A+ S7 q+ @ |& W% n
cious puberty in boys also results from inappropriate
+ Q. E& ~7 d2 [; {1 V8 A( Kandrogenic stimulation from either endogenous or5 e/ N9 V& d! T3 E% T5 W4 V; _. z
exogenous sources, nonpituitary gonadotropin stim-& r% m; ~" ]: k# S9 n, c4 |
ulation, and rare activating mutations.3 Virilizing
& `- Y1 y% b- L+ m, k+ `7 Gcongenital adrenal hyperplasia producing excessive
- ~* D9 t% _4 C+ }7 t& s3 ?adrenal androgens is a common cause of precocious
8 ^' N) x! \- x1 Npuberty in boys.3,4
5 U# q8 c) e2 o7 K- Y3 s7 L$ J" {* XThe most common form of congenital adrenal5 @* Q; [3 k2 @2 |& E# e# K
hyperplasia is the 21-hydroxylase enzyme deficiency., W& I6 q( \1 A0 R. B; Q* [# b
The 11-β hydroxylase deficiency may also result in
- v% c/ X4 U; p. ~' M: kexcessive adrenal androgen production, and rarely,
( r& E X- }1 E* z) l3 K# O' Gan adrenal tumor may also cause adrenal androgen
$ W1 K' Q( [* w3 K3 D; Hexcess.1,35 ]9 {3 K2 a0 n8 b" K+ o. ?
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from% H# i' T. ]$ P7 i. d- W
542 Clinical Pediatrics / Vol. 46, No. 6, July 20076 w+ Y) ]8 ]: _7 F
A unique entity of male-limited gonadotropin-
" O4 Q+ s' h" _# d( r+ J, gindependent precocious puberty, which is also known
" z5 _7 x m# f% `8 aas testotoxicosis, may cause precocious puberty at a# @! f4 p7 [' M
very young age. The physical findings in these boys, e2 ~. m9 z/ {, A% T
with this disorder are full pubertal development,
5 J; a$ s" _3 x+ M( U' yincluding bilateral testicular growth, similar to boys! C# z7 X9 Z. J( l b
with CPP. The gonadotropin levels in this disorder9 @$ Z7 s" z$ D. ?6 ^
are suppressed to prepubertal levels and do not show
, h; Z! |% C% [: `pubertal response of gonadotropin after gonadotropin-4 o% J! `9 F0 h6 {; Q4 V1 v$ J
releasing hormone stimulation. This is a sex-linked7 R, e) O" d( t3 r1 Y. n7 T
autosomal dominant disorder that affects only! s% k. E8 j0 ?: d8 E9 u
males; therefore, other male members of the family2 ^0 _ o. ~" l- W; Q T
may have similar precocious puberty.3& C: [1 g" K9 N- R& h0 g
In our patient, physical examination was incon-# J* I* E5 N) H9 I! T6 R# Y- w
sistent with true precocious puberty since his testi-
1 H1 Z! }5 a8 i, \cles were prepubertal in size. However, testotoxicosis
M9 \# w9 e- Q6 w4 O Cwas in the differential diagnosis because his father
7 Y! B. N$ M) V; k4 y# f4 N) Q; tstarted puberty somewhat early, and occasionally,1 W' D4 Y$ G; b: A
testicular enlargement is not that evident in the7 ]; o, n0 n. I2 I* h: q$ R
beginning of this process.1 In the absence of a neg-8 W& ^# q5 y; \2 i
ative initial history of androgen exposure, our# ]1 B" C/ W* z4 M3 L
biggest concern was virilizing adrenal hyperplasia,
6 @% z4 D Z5 V# I/ |either 21-hydroxylase deficiency or 11-β hydroxylase' {+ d" T4 B7 I% t1 Q
deficiency. Those diagnoses were excluded by find-
( o' s" e$ P$ e! _ jing the normal level of adrenal steroids.5 f( O* D6 _# G( M0 r$ g- q1 M
The diagnosis of exogenous androgens was strongly
+ e% y1 A( t/ H8 l# e7 K3 X+ {suspected in a follow-up visit after 4 months because- v! J, r* j3 g" V2 }' n* v! I
the physical examination revealed the complete disap-
8 N% k G3 V5 `6 K- Gpearance of pubic hair, normal growth velocity, and
6 o+ U; X W+ G( Vdecreased erections. The father admitted using a testos-
% U5 X, z$ b7 @+ eterone gel, which he concealed at first visit. He was9 Y. l+ G( T! w
using it rather frequently, twice a day. The Physicians’6 ]3 y; b+ r+ j, b% [, n
Desk Reference, or package insert of this product, gel or4 \5 P. W, s2 }5 E
cream, cautions about dermal testosterone transfer to! s0 C" J: J8 W' y3 f$ ~% i
unprotected females through direct skin exposure.
$ v- m8 p3 X, Q" o I5 ~. w8 wSerum testosterone level was found to be 2 times the
. _# `' U, d4 @& f* u% d X& A3 gbaseline value in those females who were exposed to
8 }; U- Z/ U% Q# veven 15 minutes of direct skin contact with their male
3 @) M, h) `4 Y7 N, B6 ^partners.6 However, when a shirt covered the applica-- w0 E& ^- a$ E D
tion site, this testosterone transfer was prevented.3 B0 \/ L! N% Y( x# X
Our patient’s testosterone level was 60 ng/mL,. I6 W# I+ G H2 i0 F/ v
which was clearly high. Some studies suggest that
# W$ G0 Z$ v4 k+ [* k) U1 p0 }dermal conversion of testosterone to dihydrotestos-
6 U* J! C% e! q6 dterone, which is a more potent metabolite, is more* l+ P+ Z2 K* [5 v
active in young children exposed to testosterone
" `6 b% W% c0 A) r# ~5 Fexogenously7; however, we did not measure a dihy-
c$ l4 t; r" r" k- m4 Gdrotestosterone level in our patient. In addition to
. E4 ~& E' U" F, K3 mvirilization, exposure to exogenous testosterone in
$ g. J, ]& }, Z1 G5 Y0 f u/ D9 Fchildren results in an increase in growth velocity and
9 S+ y( ]( z6 c7 h0 L. Zadvanced bone age, as seen in our patient.
u% [% p& {: t$ {( GThe long-term effect of androgen exposure during: {- `3 ~5 F, k4 w+ J
early childhood on pubertal development and final9 W: L# P: M# B" a
adult height are not fully known and always remain4 E; ^' c" l- S. u) j
a concern. Children treated with short-term testos-
/ }- c. ~1 a, E4 p, R4 r, R0 Mterone injection or topical androgen may exhibit some
4 C8 y6 X2 z9 j! bacceleration of the skeletal maturation; however, after! v& I' j. M1 N; U: u! @" T4 e
cessation of treatment, the rate of bone maturation: Q6 j9 ?$ D: h9 d' d/ l
decelerates and gradually returns to normal.8,9
, H0 d! E& w$ h7 TThere are conflicting reports and controversy
6 ^* u$ I( t! V8 Pover the effect of early androgen exposure on adult4 B3 O7 }9 i+ P
penile length.10,11 Some reports suggest subnormal
D1 w. w1 v$ ]/ H& ^8 ?' {adult penile length, apparently because of downreg-
/ d/ C: x7 Z4 E+ Bulation of androgen receptor number.10,12 However,
. G% z$ B: f1 G r" a6 g$ {Sutherland et al13 did not find a correlation between" Z$ K% O9 L- ~* F+ x
childhood testosterone exposure and reduced adult/ @4 [5 I8 c0 z( }/ Y
penile length in clinical studies.
2 m( ~3 l Y# X% o9 |. g9 I4 JNonetheless, we do not believe our patient is
$ E# i) m; }2 s6 K5 J9 _! T4 ogoing to experience any of the untoward effects from
" m C9 d! T3 Etestosterone exposure as mentioned earlier because
6 G7 z: `8 m" `. P6 n# w3 Zthe exposure was not for a prolonged period of time.) X* U4 d f/ N; F$ @* U6 c1 J
Although the bone age was advanced at the time of+ C/ i6 V! P( y# w
diagnosis, the child had a normal growth velocity at) w! u8 r$ h& ~7 C) m4 ?
the follow-up visit. It is hoped that his final adult3 q, f' u" g/ G# ~' B
height will not be affected.
, e3 Z: d. s7 k- a) d; G L' N# lAlthough rarely reported, the widespread avail-! I1 o3 m1 ?6 w( y" Y- v
ability of androgen products in our society may3 |8 _1 U0 x( e% M s
indeed cause more virilization in male or female
: @( A7 }9 j( o; ]$ I8 }' w" j7 Qchildren than one would realize. Exposure to andro-9 U' _! t" ?; I' `% C: Y
gen products must be considered and specific ques-
. Y" F9 X, K/ Z3 c* f! j5 [tioning about the use of a testosterone product or0 v, D1 @% n, M& s9 H
gel should be asked of the family members during5 f/ m8 C& }' ]" q
the evaluation of any children who present with vir-
( _* }7 a( K4 S! Pilization or peripheral precocious puberty. The diag-0 _4 ]. C1 X; M% |8 p3 p
nosis can be established by just a few tests and by
$ n% }6 [6 a5 B+ U& b, P, J; happropriate history. The inability to obtain such a+ J" i. I; e9 K( `% R
history, or failure to ask the specific questions, may. ]- u, G6 W: v8 \& K! M
result in extensive, unnecessary, and expensive2 @( }( g! x+ Z( k% g+ H' F6 F0 o
investigation. The primary care physician should be
8 n- t4 N& l8 e5 a' E7 u9 z" Kaware of this fact, because most of these children# Q1 K% Q& s* L7 r6 `1 W
may initially present in their practice. The Physicians’
8 T j. t1 V2 \( c, X6 v$ aDesk Reference and package insert should also put a1 f. ~0 |7 @ w- x! d* v
warning about the virilizing effect on a male or7 H0 \4 {: [4 J+ g
female child who might come in contact with some-1 w C9 n1 F }! O" b, [
one using any of these products.
/ j! k: X3 w4 ~6 u/ L; Z0 E: NReferences
3 R* S& ]) b0 B* R: S1. Styne DM. The testes: disorder of sexual differentiation. l' U! p0 F: j% w6 f* f
and puberty in the male. In: Sperling MA, ed. Pediatric
( z# \$ Z' S6 v* T7 j+ B2 u" QEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;( W, J0 R" Z3 f+ y) a/ S$ f3 ^
2002: 565-628.
, p. @1 U8 l7 S. ~$ e8 s& y2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious; l) b3 Q& B" F2 d7 S& d2 l% y7 r: `
puberty in children with tumours of the suprasellar pineal |
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