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Sexual Precocity in a 16-Month-Old, |1 p) `' v7 j
Boy Induced by Indirect Topical% p5 R p: ~# |( J. _
Exposure to Testosterone
; O8 O: E- e! eSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2% V% _( K, ~9 p% J* ]$ l
and Kenneth R. Rettig, MD1
* I! e; N2 f7 W6 i) OClinical Pediatrics
+ h7 J) R8 ^5 j2 h; [* vVolume 46 Number 69 U" u: D& {5 @* [
July 2007 540-543/ z. P; }) |8 D7 [0 G0 M7 K' X
© 2007 Sage Publications
7 [! A4 f! s: D10.1177/0009922806296651
) j9 z6 E6 G1 _1 ~2 L! `http://clp.sagepub.com4 Q6 M/ Q7 W8 {9 \: C. Q
hosted at( a; ^* u- I/ k! h# {
http://online.sagepub.com1 b7 g, y6 x* w# y6 z
Precocious puberty in boys, central or peripheral,) ?! o5 p; q; k( i( U- R7 t
is a significant concern for physicians. Central
5 u! h9 g1 \3 F5 \- F9 {+ Xprecocious puberty (CPP), which is mediated
" `1 Q, C& g* p, Zthrough the hypothalamic pituitary gonadal axis, has
5 M3 |8 w% P- L3 l4 Qa higher incidence of organic central nervous system0 P: F: X& I7 X5 z: ^2 Y/ G+ v
lesions in boys.1,2 Virilization in boys, as manifested! A9 E3 ]# w. L) ~2 ]6 O% g5 y
by enlargement of the penis, development of pubic4 v, I( j' e6 h+ ?1 M) T/ n
hair, and facial acne without enlargement of testi-6 m$ x8 T9 j/ L: N+ \3 D
cles, suggests peripheral or pseudopuberty.1-3 We
9 R$ w2 v8 R, Y xreport a 16-month-old boy who presented with the
5 P; l( F# w; g/ ?+ Z3 N% Menlargement of the phallus and pubic hair develop-
$ m# l( `1 ^( G2 O, N4 Q( n: Qment without testicular enlargement, which was due
0 V6 F8 x: |, q- L* Gto the unintentional exposure to androgen gel used by" W8 a! |# S2 ^0 C: o6 d
the father. The family initially concealed this infor-
6 _; h- K2 H0 @1 ]mation, resulting in an extensive work-up for this
7 e5 O: a* U5 m1 ? C) Zchild. Given the widespread and easy availability of
/ \% V, x8 n$ N& G- b+ k j5 Atestosterone gel and cream, we believe this is proba-
4 i9 l& a- X, Qbly more common than the rare case report in the
A `% Y! x) E+ m l6 X+ Y' @1 Uliterature.49 w6 g4 n5 d) \, Q; i
Patient Report* {( E. ~" A5 z- B& X
A 16-month-old white child was referred to the. P9 R0 v* ?7 ~
endocrine clinic by his pediatrician with the concern4 {( N! A$ O+ v
of early sexual development. His mother noticed' t0 Q; N+ T0 x8 X" F$ S" k. s
light colored pubic hair development when he was9 J% B' y; }9 Z0 R) X
From the 1Division of Pediatric Endocrinology, 2University of
x) N' E0 ]$ |South Alabama Medical Center, Mobile, Alabama.
6 E8 z' u, h' o' r6 ]& z& XAddress correspondence to: Samar K. Bhowmick, MD, FACE,
" `" w! Y# \, }Professor of Pediatrics, University of South Alabama, College of
8 j4 ~3 u6 s( b8 A) G; ` BMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
8 d( p' P8 Q* `! w! C! ?e-mail: [email protected].8 t y e W9 M1 A
about 6 to 7 months old, which progressively became
: k* o& F( O/ n' p3 ?: N+ `$ h4 Ydarker. She was also concerned about the enlarge-
, h; G8 R: n% y. xment of his penis and frequent erections. The child7 X! c2 U0 t& w; S2 J
was the product of a full-term normal delivery, with
9 @+ C: e$ y* o% k- b7 X/ {3 h9 Ca birth weight of 7 lb 14 oz, and birth length of
& F$ C1 W, B! O# B20 inches. He was breast-fed throughout the first year
5 t3 E) l3 u @8 ?of life and was still receiving breast milk along with; p& Y8 R& X" e' S9 b3 `8 d
solid food. He had no hospitalizations or surgery,
6 k3 J( Y1 U" ^/ kand his psychosocial and psychomotor development. T3 y2 I% Q4 Y+ h0 U# J
was age appropriate.
" |8 K; p& [2 ~* Y* dThe family history was remarkable for the father,
4 O8 i' ]) ^. e5 ^. c9 swho was diagnosed with hypothyroidism at age 16,* Q9 E. h8 p7 C
which was treated with thyroxine. The father’s
2 e( E0 c1 @2 w8 M% v) hheight was 6 feet, and he went through a somewhat
: P8 X) C3 N5 W1 s' Cearly puberty and had stopped growing by age 14.
7 \% j8 T1 F- H" O tThe father denied taking any other medication. The
& E& M9 K/ P$ D. T4 `8 w' P4 dchild’s mother was in good health. Her menarche
o) }1 k$ u- v* b( o2 W% pwas at 11 years of age, and her height was at 5 feet$ G) A& w* p1 [" W' |
5 inches. There was no other family history of pre-4 _9 q- o5 }: X4 U) d8 P
cocious sexual development in the first-degree rela-+ p. y- I9 I. i8 I" E
tives. There were no siblings.# a5 ^! q. X7 e# U
Physical Examination! L/ A4 d) ]) N9 E1 h
The physical examination revealed a very active,
9 I# z: t+ l/ x& Bplayful, and healthy boy. The vital signs documented
P, ~: Q% c$ e6 L5 J, K: C" y3 e' ta blood pressure of 85/50 mm Hg, his length was
9 c" O3 N3 \5 @, E7 R* d90 cm (>97th percentile), and his weight was 14.4 kg
2 b# n3 ~& Z# C9 t: @" U p+ w5 G(also >97th percentile). The observed yearly growth
- k7 P2 M3 L. avelocity was 30 cm (12 inches). The examination of5 o# q) Q4 P/ A; T0 N2 H3 Y0 a
the neck revealed no thyroid enlargement.
6 N6 M. A3 Z% X) y' E; S6 KThe genitourinary examination was remarkable for
8 Z; B6 E2 A; ]% w' Q4 ^" T( \8 benlargement of the penis, with a stretched length of
9 p' I1 P8 m5 h" D* b1 B8 cm and a width of 2 cm. The glans penis was very well
& k* ?1 y+ A# I) F9 h& Odeveloped. The pubic hair was Tanner II, mostly around
( V! ~) }7 p l540
! y' y/ c+ w$ w7 q; T* y, Jat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from4 y& n: S' s, z! x( B7 D5 \7 ]
the base of the phallus and was dark and curled. The! @+ k( a+ |: O: K& V7 B0 y8 C
testicular volume was prepubertal at 2 mL each.
& P7 h2 q4 L& H4 m# f$ m: DThe skin was moist and smooth and somewhat
& N, ~$ _+ V" d/ H/ Goily. No axillary hair was noted. There were no
0 \8 p4 R3 a/ J& L: X) T: m9 X, ^abnormal skin pigmentations or café-au-lait spots.
2 W8 H& l1 [& ^* g1 ^3 r$ j4 M0 l& \Neurologic evaluation showed deep tendon reflex 2+: t* |; \1 g8 f: W
bilateral and symmetrical. There was no suggestion
4 _ f( n/ K3 t+ |! bof papilledema.
/ F; D. n- ?3 J! j6 cLaboratory Evaluation
* P! L1 q, ?% [+ jThe bone age was consistent with 28 months by
/ r! d( q4 d# K K5 O& iusing the standard of Greulich and Pyle at a chrono-
7 N, b2 P3 n/ X! Hlogic age of 16 months (advanced).5 Chromosomal
' S( d8 j- L! f/ b1 Z, | Wkaryotype was 46XY. The thyroid function test
) h+ Z* e% v7 P3 S, k2 h7 @3 \showed a free T4 of 1.69 ng/dL, and thyroid stimu-5 z$ K! N) s& n; | Y. l
lating hormone level was 1.3 µIU/mL (both normal).8 B' _6 g, |, X
The concentrations of serum electrolytes, blood5 x4 |" l9 r) m# ~. h3 u) g
urea nitrogen, creatinine, and calcium all were
* B0 Z, N4 |3 q, c, F8 b+ Swithin normal range for his age. The concentration6 v( A/ K* C2 V) l- Y- b3 A6 {
of serum 17-hydroxyprogesterone was 16 ng/dL
) k! V0 n3 E( a" U3 G. y7 z/ A(normal, 3 to 90 ng/dL), androstenedione was 20
; s$ M8 V0 ?8 s* {8 \ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
3 L6 I/ @) J! i$ e7 M' u: b2 ^terone was 38 ng/dL (normal, 50 to 760 ng/dL),
' u% G" Y. ~& O) A5 D# i( \desoxycorticosterone was 4.3 ng/dL (normal, 7 to- b9 ~* x3 k" F
49ng/dL), 11-desoxycortisol (specific compound S)
, H {7 P8 h. E" n3 A6 b9 x. I/ Jwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-! w, a6 [: r# ^6 P# F: s
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total4 \4 `: v$ Z4 l/ Y" c5 }5 I9 d
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),, S, H, i# b! X" j, t( o
and β-human chorionic gonadotropin was less than
( [; G% J. y' r" r% N+ H9 ^5 mIU/mL (normal <5 mIU/mL). Serum follicular/ g, e6 F+ {% R0 @$ W
stimulating hormone and leuteinizing hormone
8 }" }$ R4 ~* i2 {concentrations were less than 0.05 mIU/mL
0 h* {3 S+ @1 D8 e0 m6 J$ i(prepubertal).% C+ {7 j l/ n3 }9 S
The parents were notified about the laboratory c. S4 t+ p! E& y! P" u
results and were informed that all of the tests were: ]* |/ M" ]( T0 u2 r3 F* R& a
normal except the testosterone level was high. The
- I1 A2 x( S% W `# {* h; [follow-up visit was arranged within a few weeks to9 n/ `+ r2 |: h: t
obtain testicular and abdominal sonograms; how-# N4 l$ _2 e! p, z8 a4 R
ever, the family did not return for 4 months.
& [7 x% v* k0 H; w8 ^/ OPhysical examination at this time revealed that the0 {' z: H; z* h" i3 | w* {: C- X; e
child had grown 2.5 cm in 4 months and had gained
$ p8 M, B$ [$ Y; q7 L2 kg of weight. Physical examination remained6 F+ E$ L! q1 H+ t! j7 R
unchanged. Surprisingly, the pubic hair almost com-
2 M9 c% V6 _* ~$ T+ {pletely disappeared except for a few vellous hairs at8 @+ h6 W% d$ k9 u1 M: s' s5 w
the base of the phallus. Testicular volume was still 2# e$ u2 `& ]8 w# c; ^: N
mL, and the size of the penis remained unchanged.. {+ b. T9 J' L- d u G6 a
The mother also said that the boy was no longer hav-- M6 C4 h$ k! |1 D- r
ing frequent erections.! T9 h) d U& K% _0 M( ]
Both parents were again questioned about use of
4 n. [# d! v1 z4 V2 B$ z/ kany ointment/creams that they may have applied to# S0 G' q) ~+ ^- Q# v, J4 f; Q& R0 O
the child’s skin. This time the father admitted the
0 M) u: K, X; H: ^Topical Testosterone Exposure / Bhowmick et al 5418 R5 g, a1 S3 t, _
use of testosterone gel twice daily that he was apply-
4 o$ g) ]* d& N5 `ing over his own shoulders, chest, and back area for
% V- ? ]) H* [0 R. o: Z9 m. la year. The father also revealed he was embarrassed
6 z( f6 o8 z/ ], p5 s2 `9 b* Hto disclose that he was using a testosterone gel pre-
( [ B0 k: D4 u6 hscribed by his family physician for decreased libido+ g$ w6 G$ ^/ M8 u8 w1 t1 h5 _
secondary to depression.; U1 A3 Z% t( A$ c0 B
The child slept in the same bed with parents.1 `4 q* D/ ]% t0 @0 i
The father would hug the baby and hold him on his1 t9 r" [" n7 }( M9 w9 l+ W
chest for a considerable period of time, causing sig-
. j% N5 C# v7 Mnificant bare skin contact between baby and father.- i( \* b6 B4 k. p7 U" I
The father also admitted that after the phone call,( i1 a9 H) c4 p1 |7 ?4 [8 [) S+ q
when he learned the testosterone level in the baby
8 J1 f% Z( W+ I( F$ Vwas high, he then read the product information
& i1 X1 ^' ]; A: `5 qpacket and concluded that it was most likely the rea-
# H: D! z+ l+ }, Lson for the child’s virilization. At that time, they' A. C6 c4 H/ _! v0 \
decided to put the baby in a separate bed, and the
' O. X8 }# C& X4 V1 K Yfather was not hugging him with bare skin and had( j* a2 \% w- Q3 f9 Q4 [
been using protective clothing. A repeat testosterone
: D# Y7 ]0 Z4 \test was ordered, but the family did not go to the- B2 |9 C; [/ j0 e; I
laboratory to obtain the test.
8 r0 A# f; P7 n) O( dDiscussion
+ Z4 w* k2 h' g1 {: IPrecocious puberty in boys is defined as secondary, d2 O2 C- O/ l4 ^; k9 s* a3 w
sexual development before 9 years of age.1,4
8 `& Z0 B, W8 b: w# kPrecocious puberty is termed as central (true) when! k% _/ O; W* D8 m6 d4 d, e! L
it is caused by the premature activation of hypo-8 ?& U8 H% a5 A+ q8 @. ?1 a
thalamic pituitary gonadal axis. CPP is more com-8 K' m N7 D# Q0 h) @- E
mon in girls than in boys.1,3 Most boys with CPP
t2 L. S/ `+ Qmay have a central nervous system lesion that is1 M P3 x' I- _6 C. l* `' l! e
responsible for the early activation of the hypothal-
6 L' w. E( p5 ]; |) n9 P* [amic pituitary gonadal axis.1-3 Thus, greater empha-# ]: t- R6 Z7 z2 N$ {1 t0 [9 G
sis has been given to neuroradiologic imaging in1 }4 t6 Q2 U" T& e0 m* e7 l
boys with precocious puberty. In addition to viril-
; S( N8 C3 c) A* w* q$ y7 ^ization, the clinical hallmark of CPP is the symmet-- Z0 Y% V2 T4 Y& n: ]" \
rical testicular growth secondary to stimulation by
: z1 k `- g* x- A! ]gonadotropins.1,3
: F2 @4 K2 Y* J6 T d' w! AGonadotropin-independent peripheral preco-9 c; v# S- \# k# R9 E) i. y: t, U
cious puberty in boys also results from inappropriate: y' x/ z' m9 i0 W5 G% n" W
androgenic stimulation from either endogenous or* K' l/ G5 n: l" c' W
exogenous sources, nonpituitary gonadotropin stim-5 f- ^5 j& d0 U- t
ulation, and rare activating mutations.3 Virilizing
d, B4 a2 t( Q N1 d% F+ kcongenital adrenal hyperplasia producing excessive% }/ v; K1 v) J
adrenal androgens is a common cause of precocious
0 Z1 b& Q5 J. ^: u3 zpuberty in boys.3,43 [1 T+ f G4 H
The most common form of congenital adrenal" _5 F" }. ?0 E
hyperplasia is the 21-hydroxylase enzyme deficiency.( t9 k; e+ w% Q
The 11-β hydroxylase deficiency may also result in/ G" s; ^, N1 g
excessive adrenal androgen production, and rarely,2 U4 S, @3 n+ \2 L
an adrenal tumor may also cause adrenal androgen
+ d7 S! j* U7 H& Y; Uexcess.1,3
) Q- _: G2 l9 M" c Hat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 S G" N% x% P& h! C2 Q+ B
542 Clinical Pediatrics / Vol. 46, No. 6, July 20077 M. D$ W7 m% F) @3 a8 X3 j4 A
A unique entity of male-limited gonadotropin-; }7 p7 T- L6 }2 |6 O+ T* x
independent precocious puberty, which is also known
, ?% h" F) q8 S7 @$ _as testotoxicosis, may cause precocious puberty at a) r4 V' F# e o- C4 F
very young age. The physical findings in these boys* N$ Y# c" m. J" \2 }6 F( X
with this disorder are full pubertal development,5 {# V' Z/ r0 F1 b
including bilateral testicular growth, similar to boys
, A. R- @' c. W5 D9 ?" S; Qwith CPP. The gonadotropin levels in this disorder6 N3 {7 ?1 g3 G( s+ i
are suppressed to prepubertal levels and do not show( u8 E& X5 R& ]1 S( v6 w
pubertal response of gonadotropin after gonadotropin-* u* v; w5 h5 x7 ~: b
releasing hormone stimulation. This is a sex-linked
5 Y5 q; i1 A2 W: [autosomal dominant disorder that affects only
/ A( C' u$ q7 k8 _' U* Cmales; therefore, other male members of the family8 X8 E# K) n/ |" L! m. s
may have similar precocious puberty.3/ U1 `2 a7 b( ^. a* H4 v4 I
In our patient, physical examination was incon-
) l4 y. o, A( X- o6 o6 S* Fsistent with true precocious puberty since his testi-1 ^. f, ~8 F" |7 [/ {$ }
cles were prepubertal in size. However, testotoxicosis! R8 q4 `0 z% i5 X
was in the differential diagnosis because his father
+ R; F3 k1 i2 [7 ^8 ~ wstarted puberty somewhat early, and occasionally,
, z5 w* z! D* M1 a4 S$ Qtesticular enlargement is not that evident in the6 M; X4 Q9 o; X- j) a; Y, C( ]
beginning of this process.1 In the absence of a neg-
5 N6 r- s, K9 B" Fative initial history of androgen exposure, our3 X* G' P% b$ f r% J9 t' C$ K
biggest concern was virilizing adrenal hyperplasia,
; ^& r& V# ]* O- f7 Geither 21-hydroxylase deficiency or 11-β hydroxylase* Q& y- a4 \5 Z" d
deficiency. Those diagnoses were excluded by find-6 B, Q: x3 z0 n4 Q$ A
ing the normal level of adrenal steroids.
6 |, q. f+ j: Y9 } D5 OThe diagnosis of exogenous androgens was strongly- A- j' [! J/ N* M( M
suspected in a follow-up visit after 4 months because' E! Z; Q6 U( D* H
the physical examination revealed the complete disap-* q& D! @# G W+ m# r* x4 S
pearance of pubic hair, normal growth velocity, and
, m0 P6 x$ T! Q, U1 kdecreased erections. The father admitted using a testos-* y9 @1 C) {% k3 U* W
terone gel, which he concealed at first visit. He was
- i2 ^* p8 o6 R1 d6 d1 Musing it rather frequently, twice a day. The Physicians’, s5 F. \" ~; o
Desk Reference, or package insert of this product, gel or
" Q# R4 P1 ]) Z" W5 |" F6 _, Zcream, cautions about dermal testosterone transfer to/ J- B$ L9 f+ l: ?5 K- f. [
unprotected females through direct skin exposure.
$ [9 y; L; N, G7 Q; q: C/ \9 ] QSerum testosterone level was found to be 2 times the( Y% u2 V" a0 O# t; ^8 Q- l
baseline value in those females who were exposed to
! G& d, r Y8 F9 ?% \even 15 minutes of direct skin contact with their male
$ ~; p3 ~1 O) d0 N& Rpartners.6 However, when a shirt covered the applica-* J6 |1 |; |7 s) N4 j
tion site, this testosterone transfer was prevented.
3 |' E1 _( o+ f' vOur patient’s testosterone level was 60 ng/mL,
; r5 F: G( C6 _which was clearly high. Some studies suggest that4 t9 W7 Y$ C; ?1 A% ?* X8 ]
dermal conversion of testosterone to dihydrotestos-) U" [% }# d& Q' k2 K, ^8 e
terone, which is a more potent metabolite, is more' K4 d7 Q) r# G' Q4 j: K
active in young children exposed to testosterone2 z' k$ ?( H7 }) h- s7 i5 t
exogenously7; however, we did not measure a dihy-( i1 F J$ q/ S9 Y7 A
drotestosterone level in our patient. In addition to1 `3 E$ `( y2 B7 }9 |
virilization, exposure to exogenous testosterone in( w _' X. U$ R5 R- D
children results in an increase in growth velocity and+ a/ e1 G3 F6 H8 |, k7 v) Q
advanced bone age, as seen in our patient.
- M8 I0 D7 J# x8 B2 yThe long-term effect of androgen exposure during
* ~' c4 A. @/ F" \+ |2 n: P- C. Xearly childhood on pubertal development and final( k- Y7 U: ?$ z% K+ [
adult height are not fully known and always remain
2 Q6 [ o" f5 {% Ca concern. Children treated with short-term testos-+ ~! W/ d' Z: L* `( n- a
terone injection or topical androgen may exhibit some
/ P8 c9 `+ ~' x$ l6 Wacceleration of the skeletal maturation; however, after+ `! Z! a' n' T1 W9 E$ ]9 Y
cessation of treatment, the rate of bone maturation
6 q9 l0 ~, D( ]% Y) s- s% |4 `; l$ v' O3 ]decelerates and gradually returns to normal.8,93 _8 D$ r$ Q" b9 S
There are conflicting reports and controversy
$ a2 S/ D5 a& Y! a* f7 [over the effect of early androgen exposure on adult) p3 @6 c: @+ T
penile length.10,11 Some reports suggest subnormal
% i$ {2 P" p6 {" Hadult penile length, apparently because of downreg-
+ j0 }4 A* f( P4 q `3 g) nulation of androgen receptor number.10,12 However,; p" w- K; j1 u3 F
Sutherland et al13 did not find a correlation between
9 c; M; @/ K1 ]8 Ychildhood testosterone exposure and reduced adult
1 k+ p9 f4 G/ O% V7 M8 @. L [penile length in clinical studies.
8 F) e4 G. n: ?9 |' X1 {8 B7 s: O# oNonetheless, we do not believe our patient is
' a ~( Y3 q5 g- [" G: a1 _going to experience any of the untoward effects from, ]# n. T$ ~: D, b# l5 {5 E' n
testosterone exposure as mentioned earlier because
F5 ?# n8 N5 \/ |3 mthe exposure was not for a prolonged period of time.) U3 Y9 s3 j$ X! Q8 `* [
Although the bone age was advanced at the time of* p% o! T M- |0 R/ t
diagnosis, the child had a normal growth velocity at
- q& W$ L U- V& `: lthe follow-up visit. It is hoped that his final adult
z# P! t$ S7 Sheight will not be affected.7 A" D9 m4 u! d2 F3 P- v( ~$ C
Although rarely reported, the widespread avail- T* m2 n" L0 t. T( J
ability of androgen products in our society may$ ]; m7 {4 B& e7 D7 D, H
indeed cause more virilization in male or female4 G. y% n' z7 B3 Q
children than one would realize. Exposure to andro-1 R) @, G' D/ F+ b3 ]
gen products must be considered and specific ques-. C3 Y+ H7 }) _: ]
tioning about the use of a testosterone product or
- c! q$ q' ^# Z+ dgel should be asked of the family members during7 y; X6 v1 p+ ^1 G4 p6 d
the evaluation of any children who present with vir-) l( F" Z& {% q9 {
ilization or peripheral precocious puberty. The diag-
* q; i/ u& t) g. d: H; ?nosis can be established by just a few tests and by
: p! G2 \- O+ [3 G. y* tappropriate history. The inability to obtain such a
4 A( o: p! k7 Ohistory, or failure to ask the specific questions, may+ q# n5 T( r; Q# T, g4 f
result in extensive, unnecessary, and expensive
k3 g* S% t5 l( kinvestigation. The primary care physician should be
" u5 o4 F. l7 J( Baware of this fact, because most of these children* x7 c' u! O, m1 t, E# ~5 ?( B
may initially present in their practice. The Physicians’# o3 N4 t' x' z5 r- s
Desk Reference and package insert should also put a3 i8 y$ R1 p# |
warning about the virilizing effect on a male or
4 t+ Q8 x+ j5 ?' ?8 [- r2 n/ Hfemale child who might come in contact with some-/ t1 T9 k4 l7 D$ U3 y( o0 O" c
one using any of these products.$ _7 [) X. t* V* @. v" @
References \" @6 r! o, K* z2 b: I! P. Z
1. Styne DM. The testes: disorder of sexual differentiation
- u- N. N% L# L, @% T1 ^ i9 W+ pand puberty in the male. In: Sperling MA, ed. Pediatric ^) U" v! R7 R; K0 \
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;+ Q: X8 Y+ _! q! V; e
2002: 565-628.
0 T4 D9 V) ] v$ L! ^9 C6 v0 O2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
! u( X7 R6 r) X9 z% e, e7 npuberty in children with tumours of the suprasellar pineal |
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