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Sexual Precocity in a 16-Month-Old
: ~4 G2 t+ B1 h! t* |% |Boy Induced by Indirect Topical6 }; L b* T2 o
Exposure to Testosterone
5 v) ^1 s8 w% Y Q9 G* uSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
# ~/ ]- v9 P4 }2 Q% K! Nand Kenneth R. Rettig, MD1+ m( _% S* Z O2 o
Clinical Pediatrics
* J5 A c5 N2 x# [1 i$ U2 q! M hVolume 46 Number 6
7 R2 s+ B/ ^5 t" ?& d; S3 cJuly 2007 540-543
: K; A+ ^( f! Q, [1 o% t© 2007 Sage Publications
3 G0 N# f% r4 j# I10.1177/0009922806296651/ a; Q& |( p; I+ q! s+ H# \. O2 G
http://clp.sagepub.com0 n# V$ ~# z% o3 l; r; J' f
hosted at
( x8 u3 H8 j9 ihttp://online.sagepub.com! m! R% p8 {* E8 g& Q
Precocious puberty in boys, central or peripheral,
5 r7 R" ]9 I2 _* |; Uis a significant concern for physicians. Central/ s( P1 e1 Y) S0 k
precocious puberty (CPP), which is mediated7 f) |) u# R& i x. ?+ F& o
through the hypothalamic pituitary gonadal axis, has
I( C! D$ C3 N! r( W5 B# o2 La higher incidence of organic central nervous system* G! }9 D$ C# P7 S! v
lesions in boys.1,2 Virilization in boys, as manifested
2 U1 a( M- J8 Zby enlargement of the penis, development of pubic
+ D$ `, P$ H- K5 k; ghair, and facial acne without enlargement of testi-$ N- E" p5 r2 ]1 F* K: V* E
cles, suggests peripheral or pseudopuberty.1-3 We8 ^; ^7 g6 \, O* ?' }
report a 16-month-old boy who presented with the! ~( \* A3 @& G, E/ | t
enlargement of the phallus and pubic hair develop-
' Y& ^- f/ n( p9 d0 gment without testicular enlargement, which was due
7 n. g7 ^& \ ]9 O* Rto the unintentional exposure to androgen gel used by
' v1 ~1 r3 ]/ A/ A1 bthe father. The family initially concealed this infor-$ F$ y8 \4 L7 j: [0 |/ G
mation, resulting in an extensive work-up for this
" ~1 }/ |" p8 S7 rchild. Given the widespread and easy availability of) [8 Y2 j# R, \7 a) @: l
testosterone gel and cream, we believe this is proba-
( I, }. s' |+ U, B: lbly more common than the rare case report in the: Y4 G! O' _& d7 l3 ~* j9 C7 M" T
literature.4
7 }% l+ C. C; a" s9 S. G* QPatient Report% Z$ P. ^1 f4 W: t" o/ u
A 16-month-old white child was referred to the
, L( _5 ]6 K4 j2 `endocrine clinic by his pediatrician with the concern E) C( o' w. R& d4 ?
of early sexual development. His mother noticed
, F2 |+ n2 s o7 ?7 w* Z6 dlight colored pubic hair development when he was. U) n0 w9 y3 k! r$ V
From the 1Division of Pediatric Endocrinology, 2University of- y5 E: S! }, b3 k9 k* p$ V6 Q
South Alabama Medical Center, Mobile, Alabama.; f% t: X% f: A4 p/ j" V: a1 G+ S5 K
Address correspondence to: Samar K. Bhowmick, MD, FACE,/ ?# w! O- j4 [" ?, K
Professor of Pediatrics, University of South Alabama, College of
3 V+ g$ {" L* j5 {/ m" }8 \6 e' ]Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;# Q0 ?: R1 R# V/ f; E+ n. I) O
e-mail: [email protected]., [8 m3 U6 d$ a0 |
about 6 to 7 months old, which progressively became
- e8 ?+ A: k$ n- F* N! y) Udarker. She was also concerned about the enlarge-: I* y5 o9 N' Y$ |4 F& a8 i8 Q
ment of his penis and frequent erections. The child+ d/ K! g) M( t8 Y$ k
was the product of a full-term normal delivery, with
' e7 \$ q4 H6 M* d7 ba birth weight of 7 lb 14 oz, and birth length of
/ Y; S5 X, p$ x: D) G1 Z20 inches. He was breast-fed throughout the first year
6 a, ]9 s6 r, c* P9 H Eof life and was still receiving breast milk along with' ^" U3 F9 b- ?
solid food. He had no hospitalizations or surgery,
# ?+ u, W5 s/ `* n. j# aand his psychosocial and psychomotor development
2 T% N5 k- ~) Kwas age appropriate.
. Q/ J v* ~$ ^0 G* U& `The family history was remarkable for the father,1 E+ w/ n x& F+ f \3 e
who was diagnosed with hypothyroidism at age 16,* V ^3 q8 L" Z& ^! l
which was treated with thyroxine. The father’s
2 f% @/ m9 u" v/ M3 kheight was 6 feet, and he went through a somewhat$ P! p2 i5 G. Q5 a# @5 h
early puberty and had stopped growing by age 14.
" y; t/ r( `8 | L/ _The father denied taking any other medication. The
6 `2 i0 [- {5 `. v: Kchild’s mother was in good health. Her menarche
/ y6 @/ [+ ?. w, N* \9 Awas at 11 years of age, and her height was at 5 feet
; O; o6 S) \" }: h" f6 n* J5 inches. There was no other family history of pre-
' f4 Z6 G2 L ecocious sexual development in the first-degree rela-+ E" M& B1 i. V- ?$ E; U+ i
tives. There were no siblings.
3 P; t0 x5 E2 X% TPhysical Examination
6 J H/ G$ O2 _% J, {) P- |The physical examination revealed a very active,! x; m' S/ _$ S3 y8 I/ w6 S& c
playful, and healthy boy. The vital signs documented
: T7 c, X1 A& G. j; ]9 M* \1 Ga blood pressure of 85/50 mm Hg, his length was
$ u3 ?1 b2 i9 z# U! c9 t90 cm (>97th percentile), and his weight was 14.4 kg+ m# E- ?% ?3 ?, |
(also >97th percentile). The observed yearly growth
0 K F1 }, \& evelocity was 30 cm (12 inches). The examination of
: t- }5 f# d" X- Rthe neck revealed no thyroid enlargement.
' G# A8 M0 n, }1 r0 r3 a. r2 D' f0 P7 GThe genitourinary examination was remarkable for/ L3 z& M1 J8 U
enlargement of the penis, with a stretched length of+ ^! K/ {/ G9 O& l# u; p
8 cm and a width of 2 cm. The glans penis was very well
; L7 i$ e1 T/ v& P! k+ Vdeveloped. The pubic hair was Tanner II, mostly around3 [. O! y1 g8 B9 E2 R2 I
5403 S; g& ^, ~8 l: S2 G6 \, H" `( S
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from3 o2 ~! j4 ^1 P; I7 T
the base of the phallus and was dark and curled. The
( I, P+ {, b" B! d9 `testicular volume was prepubertal at 2 mL each.- C6 k& F0 r* r7 d7 j
The skin was moist and smooth and somewhat
( L' E' s5 g6 f+ s" v- Zoily. No axillary hair was noted. There were no! N* ?5 m8 Y2 S
abnormal skin pigmentations or café-au-lait spots.
6 I" Y% j+ l# t9 p M; k! M% WNeurologic evaluation showed deep tendon reflex 2++ g9 d* N+ V* [- D- q
bilateral and symmetrical. There was no suggestion& b) ]# ]( T/ \7 W5 H$ e) g# g
of papilledema.
. a: H N, L/ i) R+ v' Q# r; PLaboratory Evaluation
3 t+ E* p& h- D/ ^The bone age was consistent with 28 months by
7 L! n6 Z4 d) `6 N' C0 F' \: uusing the standard of Greulich and Pyle at a chrono-, z2 p+ M: m2 ]; e+ y
logic age of 16 months (advanced).5 Chromosomal
1 n' U2 g& X5 zkaryotype was 46XY. The thyroid function test2 O9 l0 J ?- q" j
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
$ C7 x6 r e$ olating hormone level was 1.3 µIU/mL (both normal).
3 B! U8 x' p2 F- V: U, w: t# f/ ?The concentrations of serum electrolytes, blood' |; Q1 c) n& m* B/ m
urea nitrogen, creatinine, and calcium all were
- @+ k* Y" h7 @# k2 awithin normal range for his age. The concentration
u/ M0 E4 U. lof serum 17-hydroxyprogesterone was 16 ng/dL) P, b! B0 F X7 B
(normal, 3 to 90 ng/dL), androstenedione was 20
5 x. m/ N& g8 {6 E! k- A9 Eng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
( A, B( T1 N4 dterone was 38 ng/dL (normal, 50 to 760 ng/dL),
7 S4 Y7 }6 x% u+ ^( ]6 E7 Udesoxycorticosterone was 4.3 ng/dL (normal, 7 to7 Q5 p1 g h1 A& f# a2 q
49ng/dL), 11-desoxycortisol (specific compound S)
$ N/ j+ _) l. A3 n$ d* m+ h s1 J- Cwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-! U7 u: O _8 E7 w# y e
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
- c7 Q5 O; G0 I8 ~( B) g3 xtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),0 g$ n! h' d6 t% P# r% H& t4 ^
and β-human chorionic gonadotropin was less than0 a2 @! O/ f. h' \, A
5 mIU/mL (normal <5 mIU/mL). Serum follicular O' v- _ n! r) P; ^ A
stimulating hormone and leuteinizing hormone
- y R4 L4 W% }2 a: L5 S. d4 \concentrations were less than 0.05 mIU/mL
8 z: ]: `) r' L; V2 G- S3 o) K(prepubertal).2 J+ W& o, r/ Y+ j9 D5 w6 |
The parents were notified about the laboratory" P9 @6 _) A1 K) ^+ S+ d6 S x
results and were informed that all of the tests were9 q& T8 r: g% T* u
normal except the testosterone level was high. The
7 w- |1 G# x# d o7 G: ]follow-up visit was arranged within a few weeks to3 R% s, y: c6 r3 |$ j1 [
obtain testicular and abdominal sonograms; how-9 t8 P* r4 I" [6 U+ J& Z
ever, the family did not return for 4 months.
5 v5 z$ |8 g( s7 }Physical examination at this time revealed that the
7 ]) k; K$ g. ]4 D$ v# ^- f: z7 uchild had grown 2.5 cm in 4 months and had gained
9 W* L) }6 \3 t, L) T( g# o2 kg of weight. Physical examination remained# l' X" V: d' S* L. }# g
unchanged. Surprisingly, the pubic hair almost com-
; E' e+ j C# G- d0 Lpletely disappeared except for a few vellous hairs at
- r" Q( ]2 S5 o+ Ithe base of the phallus. Testicular volume was still 2
+ ], @. {+ a3 Q4 M! WmL, and the size of the penis remained unchanged.! `4 I1 B, E3 g
The mother also said that the boy was no longer hav-
6 b; Y, \' R4 H5 x9 Ding frequent erections.
* x6 e* ?0 E' X* SBoth parents were again questioned about use of
$ Y! e$ E6 |: p( P2 wany ointment/creams that they may have applied to
- H9 o5 P0 z* R9 e4 Fthe child’s skin. This time the father admitted the
( z; m: x# A: u4 f+ h2 j% ATopical Testosterone Exposure / Bhowmick et al 541 e3 x5 `# R% m) H" w
use of testosterone gel twice daily that he was apply-
9 e. M* e! {, p- L% E, sing over his own shoulders, chest, and back area for r: n+ X6 b4 F: P1 v
a year. The father also revealed he was embarrassed
( m9 v3 ^; B3 U7 }8 J Y# j2 cto disclose that he was using a testosterone gel pre-
/ q9 P- `& H! O0 D: hscribed by his family physician for decreased libido
+ I, N6 U% n6 B5 X7 S3 L6 esecondary to depression.7 x; V% S7 [ G9 Z7 ^
The child slept in the same bed with parents.
* ~) l% F- I; Z) E# N7 {+ nThe father would hug the baby and hold him on his% q5 \( J; a5 R
chest for a considerable period of time, causing sig-
0 S4 R6 R$ Y+ H' o8 rnificant bare skin contact between baby and father.0 \" R0 z* B" r* e* U
The father also admitted that after the phone call, M/ o+ ]( x% P" @$ p$ c
when he learned the testosterone level in the baby
; r+ u; f" A5 b9 `was high, he then read the product information
6 M7 {7 ]2 V0 o% k* G- w- o2 ]packet and concluded that it was most likely the rea-! m# @5 F3 @+ Q$ f8 A% \1 e
son for the child’s virilization. At that time, they
8 `/ v. o9 v) K" Fdecided to put the baby in a separate bed, and the) i2 @+ m7 v" U" I8 \
father was not hugging him with bare skin and had( W3 s) P; M' _* Y9 G
been using protective clothing. A repeat testosterone8 Q, P; d, M7 Y" z& L a
test was ordered, but the family did not go to the
) o. N, \# o5 t4 mlaboratory to obtain the test.- I. N* x- Q7 i+ P3 v
Discussion6 X9 r7 Q, d7 h5 O5 c
Precocious puberty in boys is defined as secondary, ] C% j& z' |, b8 e3 y, p3 K5 o9 X% k
sexual development before 9 years of age.1,4' J' H. D/ C# B$ Y* L2 ~
Precocious puberty is termed as central (true) when$ u- f6 F5 J6 s* l" C. V, d" g$ P4 ?
it is caused by the premature activation of hypo-
. \+ T. B! L9 e" Z6 p$ Fthalamic pituitary gonadal axis. CPP is more com-
, t3 B% Z' Y- v3 H8 ymon in girls than in boys.1,3 Most boys with CPP
$ a$ L$ c% N$ P, |may have a central nervous system lesion that is, Z+ M6 Q" Y; L9 |6 q: {5 m9 f
responsible for the early activation of the hypothal-
' t7 S/ m' m: U( X# Wamic pituitary gonadal axis.1-3 Thus, greater empha-
1 U8 q8 M* P$ {4 r" F$ N7 Jsis has been given to neuroradiologic imaging in
7 O2 }) H9 k j4 a; l4 @boys with precocious puberty. In addition to viril-
) t0 [6 v0 ?( T. s/ \" Y3 vization, the clinical hallmark of CPP is the symmet-
7 W/ o, |) H8 {$ Z! B6 |% vrical testicular growth secondary to stimulation by
2 |5 D: p! o' Bgonadotropins.1,3
- k: U. c5 ^3 Y8 x6 @Gonadotropin-independent peripheral preco-
6 R+ B6 P3 n5 F* jcious puberty in boys also results from inappropriate
1 L1 p! y: [# v1 Q( R5 C% Vandrogenic stimulation from either endogenous or! i" ~/ q3 L0 Z/ T9 ?
exogenous sources, nonpituitary gonadotropin stim-- d5 X8 G8 t; n+ \6 G2 n
ulation, and rare activating mutations.3 Virilizing, T( f8 V( Q3 T/ k B9 [
congenital adrenal hyperplasia producing excessive
3 k& P' u9 y- J" Kadrenal androgens is a common cause of precocious' p! q( Y3 `1 u( s# k' s8 k, I
puberty in boys.3,4: N+ }- w6 W! X) B* I. s
The most common form of congenital adrenal2 T! L7 m3 t" J/ C6 F5 |& [
hyperplasia is the 21-hydroxylase enzyme deficiency.7 m5 l9 p& B4 s. Y! c( h5 n
The 11-β hydroxylase deficiency may also result in
, w: a9 j* _0 z Uexcessive adrenal androgen production, and rarely,
: W; {$ |/ a/ c+ z$ Aan adrenal tumor may also cause adrenal androgen
1 U( y0 {5 x6 {, T: F6 f, ^: l/ M% }$ uexcess.1,3* k) }" _; M* Q7 U% E; Q
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
& `7 {9 b/ x6 F+ L) d5 _( F542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
: x3 q9 Y6 h' q, N: Y: H( n; f- j( UA unique entity of male-limited gonadotropin- O" C6 _+ X2 `! R6 B$ e. F
independent precocious puberty, which is also known- _" r' j8 X* D$ n& ?
as testotoxicosis, may cause precocious puberty at a/ x; w* K: n( @' M
very young age. The physical findings in these boys J* y6 P6 Q: |, _& A
with this disorder are full pubertal development,
( T/ T; }* s( S/ @) Wincluding bilateral testicular growth, similar to boys
" u8 J& F/ W" ]/ hwith CPP. The gonadotropin levels in this disorder) p' X! R, }' `5 J/ @8 D6 Q }# e
are suppressed to prepubertal levels and do not show
# ^( V( R' ^% ]& W4 Ppubertal response of gonadotropin after gonadotropin-* _; |9 i, m' O4 b
releasing hormone stimulation. This is a sex-linked" @) |: I2 i' J G7 j" D u; Q
autosomal dominant disorder that affects only
2 \( b* C7 O* ?& w9 gmales; therefore, other male members of the family
/ J: g. c/ v N! q2 k1 P: Cmay have similar precocious puberty.3
) d; R' ?7 u! ^In our patient, physical examination was incon-
# P. x# B3 {6 P% A/ e5 I9 Qsistent with true precocious puberty since his testi-
7 n; U) V! m! [2 u1 h" `cles were prepubertal in size. However, testotoxicosis
: X, R1 _( C5 q( Awas in the differential diagnosis because his father
; j3 r- ^; C# ?0 n( d/ l; u/ F7 ]started puberty somewhat early, and occasionally,
4 Z6 `1 l4 |& Y/ Utesticular enlargement is not that evident in the, g) o* a7 {4 {% ~) i3 }% y& N: L
beginning of this process.1 In the absence of a neg-
; U. J' k0 y: L6 [! kative initial history of androgen exposure, our
4 z. v+ x$ J# l- ?$ Z- qbiggest concern was virilizing adrenal hyperplasia,
9 ]5 A! k7 q5 d, I% ]7 w* Ceither 21-hydroxylase deficiency or 11-β hydroxylase
$ z) J3 r! }0 T8 |, ]deficiency. Those diagnoses were excluded by find-
* |% o3 d+ l M8 ^8 a' ying the normal level of adrenal steroids.. Z' ~$ i* i6 m& B
The diagnosis of exogenous androgens was strongly
$ }$ w( p1 C) Y/ `suspected in a follow-up visit after 4 months because
' H0 ?9 q) G2 g2 {' b" zthe physical examination revealed the complete disap-
6 C$ |' B- q. M1 ^; q3 Bpearance of pubic hair, normal growth velocity, and
0 j' ~, z7 O3 J1 X7 u$ C8 V8 G. L/ _decreased erections. The father admitted using a testos-2 g! @ C, ]! P4 u2 O: B
terone gel, which he concealed at first visit. He was2 e9 z/ V3 M: L0 A( ^
using it rather frequently, twice a day. The Physicians’
: r% C$ V' h( T/ o% b+ L" jDesk Reference, or package insert of this product, gel or
, P7 S+ P' C7 y# C3 [$ V4 f8 u3 fcream, cautions about dermal testosterone transfer to
- T+ Z) O* v- |# X/ N/ Gunprotected females through direct skin exposure.) H) h8 h6 [/ g
Serum testosterone level was found to be 2 times the, C0 J' `1 F) d1 z
baseline value in those females who were exposed to
0 K8 J% @7 M; @' t" B# ^even 15 minutes of direct skin contact with their male" s0 t, c8 @- g- F# ]6 b& s
partners.6 However, when a shirt covered the applica-) r2 k6 F7 S4 r! r5 ~9 {* k
tion site, this testosterone transfer was prevented.
, _6 l0 s" D1 y' `; Y$ D- N- x3 tOur patient’s testosterone level was 60 ng/mL,
' Q. {7 h: Q1 w- Pwhich was clearly high. Some studies suggest that! n; K7 u9 B; z9 a$ u
dermal conversion of testosterone to dihydrotestos-" F; Y+ B i( }8 D, v) q0 G3 f Z5 a
terone, which is a more potent metabolite, is more
$ a; s8 Y% N1 G2 ]active in young children exposed to testosterone" p1 v0 R. A1 T9 `# b$ z) [: K9 j
exogenously7; however, we did not measure a dihy-5 }* Z d, X" |
drotestosterone level in our patient. In addition to u7 c: o. I5 y1 N
virilization, exposure to exogenous testosterone in
) S. Z7 |5 c1 K) y$ P2 Z, x' \children results in an increase in growth velocity and
7 i G9 e+ d6 H: Y$ c( c4 Fadvanced bone age, as seen in our patient.
6 h+ [8 g. A% ]1 kThe long-term effect of androgen exposure during4 A, k8 v7 @- I
early childhood on pubertal development and final+ ], y9 O2 M/ I( B* b6 D
adult height are not fully known and always remain/ N5 y2 g! r* E p4 C
a concern. Children treated with short-term testos-1 [5 H& k. O0 O) [1 ?6 c' Y
terone injection or topical androgen may exhibit some
/ `' W9 d: }2 F' H% N0 a2 V2 Yacceleration of the skeletal maturation; however, after
) {# ?5 N( y. z9 N# U" Icessation of treatment, the rate of bone maturation6 U% Z: p+ n' ^+ x5 ~
decelerates and gradually returns to normal.8,9 J+ a; m/ s' M. x& n! R$ z Q1 s
There are conflicting reports and controversy; `0 v2 L4 h* A7 P; f8 m
over the effect of early androgen exposure on adult) d1 a w$ q: t3 k
penile length.10,11 Some reports suggest subnormal
1 k; d* t+ N7 S' \7 c) o: N) cadult penile length, apparently because of downreg-' Y# z i7 N- w3 l) n* x0 Y
ulation of androgen receptor number.10,12 However,! @. _0 [# o9 a1 v8 ]
Sutherland et al13 did not find a correlation between' W6 ?( g. U2 [2 J: @& v8 c
childhood testosterone exposure and reduced adult2 \6 p6 o: c2 D9 H+ h2 b& s+ y9 I1 J/ L
penile length in clinical studies.
6 k: D" q7 U# |! r0 ~Nonetheless, we do not believe our patient is
1 B, P7 {; k1 c8 O2 B, @" f2 Ggoing to experience any of the untoward effects from% f) F% S4 k" F9 y h9 U
testosterone exposure as mentioned earlier because2 G$ B: V ]' y' I+ [
the exposure was not for a prolonged period of time.
) z- w$ p2 ]# dAlthough the bone age was advanced at the time of
7 d( z( T4 Y6 w% c4 E3 Xdiagnosis, the child had a normal growth velocity at) o }+ j9 @( A* L# ]. F
the follow-up visit. It is hoped that his final adult
/ b+ {* N, o6 c; |height will not be affected.# w+ Z, N: U" M+ R8 I
Although rarely reported, the widespread avail-
- u% S) E. \# L/ P0 e8 yability of androgen products in our society may
; w& b2 n$ h7 T* x! Nindeed cause more virilization in male or female9 k3 j) [: v. v7 e0 o
children than one would realize. Exposure to andro-
& V* F# ^7 O- P6 r4 Ggen products must be considered and specific ques-
7 e9 s; h+ y. w1 i8 ~# Q$ o# R- ~tioning about the use of a testosterone product or( X4 ?( ~3 v T0 _# {9 a9 m2 b: a
gel should be asked of the family members during3 K. J, t4 a3 h6 W) z
the evaluation of any children who present with vir-6 s6 y$ C- w" F2 I" x/ h
ilization or peripheral precocious puberty. The diag-1 l* P+ L( s+ T, p/ O2 t
nosis can be established by just a few tests and by
0 v2 ]1 M4 Q1 Oappropriate history. The inability to obtain such a
* L6 J* n4 O7 e% k) \4 I( Fhistory, or failure to ask the specific questions, may/ h5 v1 c2 F3 b3 S1 c! }# j! M! ~
result in extensive, unnecessary, and expensive
* c8 A. K4 s& t5 D) F: l; @investigation. The primary care physician should be
% O+ H* A3 P& E; `aware of this fact, because most of these children$ m! U) H4 v: e3 @% m4 g
may initially present in their practice. The Physicians’
8 ~3 W5 o9 \) hDesk Reference and package insert should also put a
& T/ U! _5 b+ F7 Y' [& ~1 p7 ~: D' Zwarning about the virilizing effect on a male or1 |. i3 k& H/ [* S+ f, x
female child who might come in contact with some-9 I+ `4 u) a) ] ?" T
one using any of these products.
- A; c$ \; B# KReferences# H p; \- `/ D6 A
1. Styne DM. The testes: disorder of sexual differentiation" l" g' {$ I: [ I7 T" J
and puberty in the male. In: Sperling MA, ed. Pediatric. N7 a2 y! G5 Q Y1 I, h; q7 r
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;. S: I- V; V, ^+ C
2002: 565-628.9 A9 {8 d0 A! Z7 Q+ _7 |) i/ X
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious* U$ H( X$ L% C: i
puberty in children with tumours of the suprasellar pineal |
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