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Sexual Precocity in a 16-Month-Old
: p ~, q$ @! M! A( eBoy Induced by Indirect Topical
; x+ c. G4 {, L5 F7 W) ZExposure to Testosterone
- x- f* B8 t: ]+ \Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2: w& I0 K- x) N6 X+ ?: X! Q
and Kenneth R. Rettig, MD1
4 @, _' e7 b' s2 _ {+ iClinical Pediatrics
% B/ q* b0 z" QVolume 46 Number 6
/ ^% B" A9 L/ J( W) O& iJuly 2007 540-543
# ~" _4 B7 H7 _3 p- a- r5 \© 2007 Sage Publications5 d3 F+ X: n; y4 W6 q2 C' q! P0 Y
10.1177/00099228062966512 g, x/ m. ?& {. |
http://clp.sagepub.com2 n9 _, _: C0 r3 }2 M; ]
hosted at
$ I9 b8 `5 z" `" b2 [1 @, y8 Yhttp://online.sagepub.com
: P# g2 i. D9 c( v' U q5 a8 VPrecocious puberty in boys, central or peripheral," y, [6 Y% K& W8 Z! Z
is a significant concern for physicians. Central
* v8 R1 m% `0 g( J1 ?+ h) ]precocious puberty (CPP), which is mediated
( s: W2 n4 u4 h+ U1 U3 Ithrough the hypothalamic pituitary gonadal axis, has
- F! ^6 X3 V. k! x$ j4 j9 ma higher incidence of organic central nervous system# @) H+ s0 |4 K2 e/ N, N( m8 I
lesions in boys.1,2 Virilization in boys, as manifested
% \+ H( S9 I( j, Mby enlargement of the penis, development of pubic+ p) h8 s3 w' }* i
hair, and facial acne without enlargement of testi-) t$ {( h7 M) K9 h4 g6 `
cles, suggests peripheral or pseudopuberty.1-3 We
, H8 }/ b" A/ x, vreport a 16-month-old boy who presented with the$ [, X! a% F1 @
enlargement of the phallus and pubic hair develop-# a' o/ K2 c2 G4 L j6 L/ o
ment without testicular enlargement, which was due
: \+ Q6 @( H, u( O5 q% w( Nto the unintentional exposure to androgen gel used by
. I$ F% H0 w# Uthe father. The family initially concealed this infor-
5 e2 K& S: ]5 L4 o4 N1 D9 Kmation, resulting in an extensive work-up for this
) |4 Y+ R; D k: c7 |- p; w. H3 Gchild. Given the widespread and easy availability of
: v" N2 ^% T$ G( Ytestosterone gel and cream, we believe this is proba-* V7 m5 U7 p, v8 v: V
bly more common than the rare case report in the- G/ i; a% m# ?
literature.4. s. e0 w7 [5 ?5 H8 h, G' ?
Patient Report! G( v/ t" e* v1 p
A 16-month-old white child was referred to the! O4 L- ~' y( o9 R( |9 y0 z, | Q! E
endocrine clinic by his pediatrician with the concern
9 j) n& ?9 j# ?& pof early sexual development. His mother noticed( F$ Q1 |( z$ H; X2 d$ u# w- O
light colored pubic hair development when he was) N, T9 W; L4 M G, w
From the 1Division of Pediatric Endocrinology, 2University of) m% h; K& R, H3 z) J' r- [
South Alabama Medical Center, Mobile, Alabama.7 |5 U0 m; N9 J
Address correspondence to: Samar K. Bhowmick, MD, FACE,
* X" x& d; I* [ oProfessor of Pediatrics, University of South Alabama, College of
# P! \& B. @: l* H1 gMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
* X7 J1 Y( k- g' O; A2 ]7 We-mail: [email protected].
' l8 X& n5 @/ Fabout 6 to 7 months old, which progressively became
# @" Y0 n" F. |8 d( G5 t; Qdarker. She was also concerned about the enlarge-
, l( D, U9 E! e4 e2 E1 {% Ament of his penis and frequent erections. The child& U) F9 x1 B: w* F" ?
was the product of a full-term normal delivery, with9 v( b, m) Z/ U) W7 X6 W1 }4 R' `# w
a birth weight of 7 lb 14 oz, and birth length of$ ?1 q; H8 ]9 W$ Z
20 inches. He was breast-fed throughout the first year
2 L) u" y1 Y2 l6 \( ^0 Uof life and was still receiving breast milk along with" k$ k$ A- |! P e3 H. b
solid food. He had no hospitalizations or surgery,
# s* x8 z0 v: u5 {5 [and his psychosocial and psychomotor development+ ?( {7 |) B9 P2 |$ a- y
was age appropriate." B |" {: R5 p7 e
The family history was remarkable for the father,
5 l; m% Z7 w6 X! I* v0 `who was diagnosed with hypothyroidism at age 16,& p% p7 i8 N2 q- {4 c/ K
which was treated with thyroxine. The father’s
' {: Q( I! r K: x2 w/ Lheight was 6 feet, and he went through a somewhat
( p) ^2 l+ j) Z1 learly puberty and had stopped growing by age 14." x. Q) s8 t/ C4 \
The father denied taking any other medication. The$ Z" D( G; ^7 u
child’s mother was in good health. Her menarche
5 }. a: N5 D+ ?# Y4 S) w v+ Pwas at 11 years of age, and her height was at 5 feet1 F' a7 V$ K3 \
5 inches. There was no other family history of pre-
2 C6 q' U7 b. V# o% e+ G( c; l6 |cocious sexual development in the first-degree rela-
& y6 B' q# {1 Z& M s% btives. There were no siblings./ G/ Q* ]( N0 V) v% I) D! y
Physical Examination
, q) h; ^& A$ V( L9 zThe physical examination revealed a very active,
+ `& p7 k7 n3 F$ q5 f1 b6 Z1 M0 Oplayful, and healthy boy. The vital signs documented
' J5 N! \& Q* ]" r& Xa blood pressure of 85/50 mm Hg, his length was
' {4 V2 ~3 E- ?* {90 cm (>97th percentile), and his weight was 14.4 kg
9 P8 Y$ a- E( M0 ^6 j+ z: k4 p(also >97th percentile). The observed yearly growth
: [5 |# Q8 C1 I y1 b! Evelocity was 30 cm (12 inches). The examination of! A: ^ A" n$ j! {; i
the neck revealed no thyroid enlargement.. E$ u$ b% W9 ?* B! N% u5 M
The genitourinary examination was remarkable for" Y9 ?& W: Q' ]/ }7 E
enlargement of the penis, with a stretched length of
+ n1 N1 U- T4 Y( d% P* q( b8 cm and a width of 2 cm. The glans penis was very well
& Z% N7 z q: X1 p/ ?! Odeveloped. The pubic hair was Tanner II, mostly around
. g7 V% z& _0 t- Y5408 @6 V4 _0 B- T8 G7 X9 V
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 |& F% w5 O6 B7 o: K9 V4 @, z9 g
the base of the phallus and was dark and curled. The2 A/ z- q" k7 D0 u) t; I9 e
testicular volume was prepubertal at 2 mL each., @$ b i& }) }8 X# L/ N, {
The skin was moist and smooth and somewhat
( }1 W4 r; Z) eoily. No axillary hair was noted. There were no5 S( {) i @, i0 C/ v5 F
abnormal skin pigmentations or café-au-lait spots.
g, v# L1 y% I* @, A4 lNeurologic evaluation showed deep tendon reflex 2+! { O9 C" V( @7 T; O
bilateral and symmetrical. There was no suggestion
% T: B# t' |+ d* A9 j5 Qof papilledema.
# D5 D( g4 B. s3 [6 LLaboratory Evaluation7 |) c. k( e- k" |. P d$ E
The bone age was consistent with 28 months by0 I+ g3 U* V8 g0 E
using the standard of Greulich and Pyle at a chrono-2 r% x$ J: P4 A7 i$ l3 s5 r i
logic age of 16 months (advanced).5 Chromosomal4 t/ |& @; ^; z% z; O
karyotype was 46XY. The thyroid function test$ x# a$ m5 u3 a
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
: U [7 r5 @1 m6 e" q1 blating hormone level was 1.3 µIU/mL (both normal)., J. o; r. |: @ I: Y& Q1 }6 K6 z
The concentrations of serum electrolytes, blood% c! s& A; B$ `4 U4 L
urea nitrogen, creatinine, and calcium all were0 }- w- B J8 q& U
within normal range for his age. The concentration( ]. X' w1 B; b; j6 p
of serum 17-hydroxyprogesterone was 16 ng/dL* H. I0 e3 {3 t/ ]
(normal, 3 to 90 ng/dL), androstenedione was 20" v) `" e5 q8 Z' n: { r9 c# E
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-. T4 Q9 C3 y2 `% k$ k
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
2 o, m8 A9 k+ r j/ cdesoxycorticosterone was 4.3 ng/dL (normal, 7 to
+ t8 Z% _/ g. @3 ?, | m49ng/dL), 11-desoxycortisol (specific compound S)
( I4 ? U/ `& ^; \9 g. ^. ~ ~5 Awas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
* y% K4 d# C) L l" Ktisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total1 x" u# u: |8 W& M+ K
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
2 j3 a8 h( v& ]& Cand β-human chorionic gonadotropin was less than
% C8 u7 v5 r4 R- W1 O5 mIU/mL (normal <5 mIU/mL). Serum follicular
# w- b$ c! [4 L. v! hstimulating hormone and leuteinizing hormone, c' F8 _$ v! M; B
concentrations were less than 0.05 mIU/mL1 Y& e" w: z5 I( O
(prepubertal).
9 }' c2 C& O8 S7 N) y# ~The parents were notified about the laboratory2 h) G6 o6 g& C' l U z* e) |
results and were informed that all of the tests were2 \9 s8 A7 d0 }4 v9 S1 ~' n
normal except the testosterone level was high. The
1 ]0 {) g* Q7 |, d8 _/ ffollow-up visit was arranged within a few weeks to
8 d# {% O: _7 O, O3 Mobtain testicular and abdominal sonograms; how-
0 s3 M: L# A# t+ ?% k! O; }ever, the family did not return for 4 months.
, \8 Y- }4 V+ g% G5 jPhysical examination at this time revealed that the
; [* V3 }3 f! vchild had grown 2.5 cm in 4 months and had gained
! t# x( U% ~% a+ s/ d5 e2 kg of weight. Physical examination remained. e0 C0 q/ n: n% e1 y
unchanged. Surprisingly, the pubic hair almost com-
$ H$ Y5 W7 @" y; K* E' I8 I# h0 \pletely disappeared except for a few vellous hairs at! t5 @0 w! ^# }4 F
the base of the phallus. Testicular volume was still 2
2 D) ~+ E* u. Q! V( W2 i& ^1 d6 fmL, and the size of the penis remained unchanged., p$ {4 E e0 d& F
The mother also said that the boy was no longer hav-9 C" H' X5 g8 p) S8 G5 {- t( s& M
ing frequent erections.
. R; ?4 \8 y' H- l8 QBoth parents were again questioned about use of: ^9 T' w$ B5 K9 K2 H
any ointment/creams that they may have applied to
+ \! H" S1 }! l7 M& P9 d6 p0 O' bthe child’s skin. This time the father admitted the
3 {% i' B, I7 R- V, B& mTopical Testosterone Exposure / Bhowmick et al 541
1 M: @& Q( R1 ]( E- [0 k5 Tuse of testosterone gel twice daily that he was apply-
! ?8 M) a- D g8 C9 E+ Xing over his own shoulders, chest, and back area for# h2 V. w: q7 B" |) y7 {
a year. The father also revealed he was embarrassed, w' N- {& {, o6 t
to disclose that he was using a testosterone gel pre-& n) B' [8 H9 a% o
scribed by his family physician for decreased libido
9 W- O. M9 N' f" Osecondary to depression.
4 @7 |" Q7 \% _: IThe child slept in the same bed with parents.
: E% U5 k* G1 Y+ w" G% \/ fThe father would hug the baby and hold him on his; t& y7 K; j# [7 C' r
chest for a considerable period of time, causing sig-- O; t$ ?& ~) S% y! d. b$ `# O
nificant bare skin contact between baby and father.
. m$ n- u! q3 o' dThe father also admitted that after the phone call,7 x' q/ z: |4 t( P
when he learned the testosterone level in the baby
- s6 u5 m' o0 J; P6 B* Uwas high, he then read the product information/ {6 ?, Q% ~1 n7 X$ ]
packet and concluded that it was most likely the rea-
5 T2 b, w g$ x. e+ [/ S# l$ V5 ~2 G' _son for the child’s virilization. At that time, they
M' ~7 n8 R" Y" O& b" Hdecided to put the baby in a separate bed, and the
) W; R9 }2 d5 b+ A4 A9 Z, Z1 efather was not hugging him with bare skin and had+ [( l T- V; f ` V
been using protective clothing. A repeat testosterone
% y# j' F6 ?! r2 Q4 u- qtest was ordered, but the family did not go to the& S/ E0 T8 d/ _; z+ n
laboratory to obtain the test.* H G# }; t0 j7 O: n
Discussion
5 X/ m7 a6 n) G4 t6 lPrecocious puberty in boys is defined as secondary( i4 l: A/ z; k
sexual development before 9 years of age.1,4: _$ U- _" }( Q7 w# D: k# E
Precocious puberty is termed as central (true) when$ s$ l# \: x' ]2 J) T8 a( y
it is caused by the premature activation of hypo-
! t6 N7 ]! W/ `! g# P6 w- Ithalamic pituitary gonadal axis. CPP is more com-
; Z! X0 T+ _$ ~0 G5 R P+ ymon in girls than in boys.1,3 Most boys with CPP
4 w5 W$ n/ u& tmay have a central nervous system lesion that is9 R+ U5 u8 {5 k t5 a
responsible for the early activation of the hypothal-5 t9 D" R# W, e1 _1 n5 r
amic pituitary gonadal axis.1-3 Thus, greater empha-6 G4 f0 Q9 x& Q" V4 s. r5 D
sis has been given to neuroradiologic imaging in
2 z1 |& i& a2 v) q: zboys with precocious puberty. In addition to viril-
% @/ j: R- u5 Q5 fization, the clinical hallmark of CPP is the symmet-
6 S" T! ~5 A- }- Y& ?& Urical testicular growth secondary to stimulation by
& s+ b5 K! m6 C0 D( b8 l+ Jgonadotropins.1,3
/ @8 s9 F+ Q) q0 W: }Gonadotropin-independent peripheral preco-
. S0 v$ ?" ]/ t: ecious puberty in boys also results from inappropriate9 R* a$ j2 } [7 j
androgenic stimulation from either endogenous or6 n" |: K6 d1 P1 v" q
exogenous sources, nonpituitary gonadotropin stim-
0 W, g0 i, p& f+ F; r" ^6 ^ulation, and rare activating mutations.3 Virilizing
& N. \. v4 m( a7 U% w$ h) Kcongenital adrenal hyperplasia producing excessive
4 v& |" o5 `) P5 f4 o( Sadrenal androgens is a common cause of precocious% q- E" [4 y T" n! ~
puberty in boys.3,4
4 w! M( T4 G; k9 Q2 sThe most common form of congenital adrenal
. ^; x3 j! W3 Q7 ~hyperplasia is the 21-hydroxylase enzyme deficiency., O% O3 o$ L5 x6 N- s% |$ x" r
The 11-β hydroxylase deficiency may also result in8 s4 P) U$ l9 x" w+ t
excessive adrenal androgen production, and rarely,. }3 o4 F$ D* W A
an adrenal tumor may also cause adrenal androgen! q- V; T2 x3 I6 b4 Z
excess.1,3% ~5 p( u0 J H9 p5 |2 ~3 o
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
/ h1 X: i. v3 o1 C) H3 F542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
8 y; z: P5 |( \* d* o/ P; Q: jA unique entity of male-limited gonadotropin-
+ _7 d4 h5 a* {$ K% d1 Cindependent precocious puberty, which is also known% b j0 m8 e& }6 f7 H
as testotoxicosis, may cause precocious puberty at a9 C4 T) c I; |$ U! |6 V
very young age. The physical findings in these boys( o0 W. g. @- G" P+ S
with this disorder are full pubertal development,
+ y# h" D, b+ K, zincluding bilateral testicular growth, similar to boys
% K# F- a ^- A; [! gwith CPP. The gonadotropin levels in this disorder
+ i- W7 ^. S4 i2 d. U- {- o9 {are suppressed to prepubertal levels and do not show
/ s8 u. T, k% \( L4 [+ Qpubertal response of gonadotropin after gonadotropin-4 x4 K: J- w9 q# K9 d% B
releasing hormone stimulation. This is a sex-linked
- s) g( `' o+ k9 c1 }7 W$ Hautosomal dominant disorder that affects only2 P4 r8 u+ d( F7 o# z& O6 U! c+ t
males; therefore, other male members of the family
- [: y6 Z, |, F9 s* rmay have similar precocious puberty.3" D- z) e. n: D0 h; w( p
In our patient, physical examination was incon-
* G9 a3 Y1 [. K. o$ l6 psistent with true precocious puberty since his testi-
) p- F. q: d3 g) I( C) Kcles were prepubertal in size. However, testotoxicosis" n$ z' a. i6 M/ v; A& [
was in the differential diagnosis because his father
: H; `! |" e6 Z" O0 T |started puberty somewhat early, and occasionally,3 J% Y2 N- V0 J6 ^
testicular enlargement is not that evident in the
( l. h' K+ }0 y) T2 f0 Y! Ybeginning of this process.1 In the absence of a neg-6 c; W4 @% o' K
ative initial history of androgen exposure, our
: Y G! ]# H/ b `9 \0 u5 s6 ybiggest concern was virilizing adrenal hyperplasia,6 l# p4 Z+ C( C% x
either 21-hydroxylase deficiency or 11-β hydroxylase
) I8 x( I, B0 [ sdeficiency. Those diagnoses were excluded by find-' K; p C6 t- _3 v0 a8 \/ L
ing the normal level of adrenal steroids.
. \- E2 N3 C6 KThe diagnosis of exogenous androgens was strongly
: I# P0 {5 r# Q, B( o& `suspected in a follow-up visit after 4 months because
7 \7 p- @3 M) s# jthe physical examination revealed the complete disap-2 x" h. |2 J' Y+ Z+ L5 |3 s- ] u
pearance of pubic hair, normal growth velocity, and
" h% Q: m7 z4 M" w) D) D# z. idecreased erections. The father admitted using a testos-. H/ K! V& t2 b3 \
terone gel, which he concealed at first visit. He was
7 a$ b$ C& J% ~; ?- ~using it rather frequently, twice a day. The Physicians’4 G1 L e( ^% B
Desk Reference, or package insert of this product, gel or6 Z1 b' N5 `: {
cream, cautions about dermal testosterone transfer to
/ d8 x, U5 z0 M5 n/ s' H) \) ounprotected females through direct skin exposure.2 d' `3 v) d5 C# z* R: h
Serum testosterone level was found to be 2 times the! L4 u8 e. W, m# Z$ \; p$ [ ]
baseline value in those females who were exposed to1 |! w2 M& W0 w8 I3 j" |
even 15 minutes of direct skin contact with their male
% ?7 N' }# i; V, ?2 Z/ M; Mpartners.6 However, when a shirt covered the applica-! d9 }, B: d) M. z# { C
tion site, this testosterone transfer was prevented.8 ?5 m' e1 {3 E
Our patient’s testosterone level was 60 ng/mL,8 i6 ~/ T3 P' |# D4 ?% X
which was clearly high. Some studies suggest that
3 I$ S3 x1 a! ^- edermal conversion of testosterone to dihydrotestos-6 M. h- w- k/ W5 ^
terone, which is a more potent metabolite, is more% }! }' o* t; i' ^, R8 M: e& ^
active in young children exposed to testosterone
( E4 d0 Q- y p, W6 u8 I& o- aexogenously7; however, we did not measure a dihy-
2 `. E6 d. A8 [0 J7 T6 Jdrotestosterone level in our patient. In addition to
- x, Y1 y# V0 C- ?: Bvirilization, exposure to exogenous testosterone in
; D' B |0 A! {+ b- u$ r% o# Zchildren results in an increase in growth velocity and" a3 H4 L! z" |# h
advanced bone age, as seen in our patient.
2 k p# y$ N( dThe long-term effect of androgen exposure during
+ {/ Q* z1 U' p- I' i+ I0 m# {early childhood on pubertal development and final) `& o, t# U& ~, d1 Y5 V- w+ T, u5 [) t
adult height are not fully known and always remain+ C8 h# n% p" m0 w. B' ^ {
a concern. Children treated with short-term testos-9 n: Z7 Z. S" t0 N- }% t: l8 I0 q
terone injection or topical androgen may exhibit some
- Q9 U, Q9 R% V, tacceleration of the skeletal maturation; however, after. n8 x- t6 Q9 E7 }! b+ i8 u
cessation of treatment, the rate of bone maturation
* h+ o$ {. M1 o- Ddecelerates and gradually returns to normal.8,9
. y8 x B! l; TThere are conflicting reports and controversy
5 s8 K3 V9 } [' F: hover the effect of early androgen exposure on adult
- S$ C: B8 a% F* m4 d( c* A7 Y' Rpenile length.10,11 Some reports suggest subnormal3 x! G( o" W; A3 }4 D. D* i
adult penile length, apparently because of downreg-
& p( y n9 S0 W* T. qulation of androgen receptor number.10,12 However,
+ P8 `- n6 x2 J# T' D, tSutherland et al13 did not find a correlation between
' G! J! e3 h: B T8 wchildhood testosterone exposure and reduced adult
. `. [1 d3 C2 A+ Openile length in clinical studies.
7 z; K9 k: {, }) l& a: p: f sNonetheless, we do not believe our patient is6 t) f8 L- b9 P" l6 [; k+ f6 K
going to experience any of the untoward effects from
& e+ j, L4 N" G% s# k% Gtestosterone exposure as mentioned earlier because
1 d: P: {: r3 |# P% V& {: Q' Y/ n [the exposure was not for a prolonged period of time.6 ~' R3 J3 p8 p$ i* @1 z) b( E
Although the bone age was advanced at the time of
# ]5 e A8 j6 I5 {" X0 Idiagnosis, the child had a normal growth velocity at
7 P8 Q9 m2 U2 B0 k& [! cthe follow-up visit. It is hoped that his final adult% z$ o, `* D, y ]
height will not be affected.
9 [% u Y- h, ^) O8 ]( H9 s, bAlthough rarely reported, the widespread avail-
3 f( G/ j O0 c5 G: p2 q+ Z7 I1 ~1 `ability of androgen products in our society may2 w2 P3 J1 ^! t4 M# t/ E0 l$ j3 _5 G$ v
indeed cause more virilization in male or female( P C9 B7 w6 G" X P$ K/ y, h
children than one would realize. Exposure to andro-
- P9 n6 D+ Z6 A& j4 u4 bgen products must be considered and specific ques-. K( d! n, \- k& N6 s0 ] e3 o
tioning about the use of a testosterone product or
; O0 q! c+ ^0 p( D y' u: h: @gel should be asked of the family members during
$ Q$ w/ ?; F8 |6 x! ~the evaluation of any children who present with vir-! A; x2 z. v$ l3 N3 }" I1 a% N8 `
ilization or peripheral precocious puberty. The diag-
2 L& C- U+ C7 J) j$ Y6 y4 }nosis can be established by just a few tests and by; P" }( V% O- }/ \
appropriate history. The inability to obtain such a
" P. \5 B1 b: [: S7 Z4 R( }history, or failure to ask the specific questions, may
: T* I0 c7 l4 \1 {+ @! }. G: Iresult in extensive, unnecessary, and expensive
8 k$ o; J+ R' Q5 c% C. Hinvestigation. The primary care physician should be# e' M6 ?8 L2 E% W4 T
aware of this fact, because most of these children* G- q8 ?0 k' _+ M
may initially present in their practice. The Physicians’4 k$ [6 q% e' D- M
Desk Reference and package insert should also put a2 m! f5 x0 _1 i9 K* B
warning about the virilizing effect on a male or
) Z- P% r# A* h) S) F; Efemale child who might come in contact with some-& s" k- N0 s& z3 [! M, U
one using any of these products.
6 {; x# I% F$ ?. r4 a% B0 q) ?. [References" S" b/ I( ~$ J6 y2 X1 g5 Y6 j/ Y
1. Styne DM. The testes: disorder of sexual differentiation0 a5 x5 j' W- H; m) C
and puberty in the male. In: Sperling MA, ed. Pediatric5 k6 x) V, R& b2 U
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
1 U% {% {& S5 N; m0 R! u- e. t2002: 565-628.
5 g) @7 H1 b, F h2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious" t4 b9 A3 E) \ B5 j. o$ S
puberty in children with tumours of the suprasellar pineal |
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