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Sexual Precocity in a 16-Month-Old
9 ~' T- {9 X& T6 V1 G9 o6 wBoy Induced by Indirect Topical7 r' M$ S4 X) N7 s# D4 \5 h
Exposure to Testosterone! G' ]9 L2 _6 h
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
' ]7 Q' W7 ?: X1 I/ [+ `and Kenneth R. Rettig, MD1
1 U! u! j+ ?: b$ O" l' a0 QClinical Pediatrics8 J3 C+ b8 a6 U) H, F- G& Y" d6 K" \
Volume 46 Number 6
% |, D5 Y3 _7 q y$ ]6 mJuly 2007 540-5436 z8 Z( Q9 d1 M0 X3 c% A4 J
© 2007 Sage Publications5 Z/ `9 e0 M- w( H' L2 _, H
10.1177/0009922806296651
! y, u3 W0 g2 j1 g6 xhttp://clp.sagepub.com
1 z% z! A( y6 g+ |hosted at
" T% C! Z8 x" c4 Ohttp://online.sagepub.com0 x0 T$ r! z- X9 Y2 j3 u
Precocious puberty in boys, central or peripheral," a) w' H4 B# w) a; j& d7 I* F9 S
is a significant concern for physicians. Central! J6 H! K% @$ t3 }' w- k) E) }% Z
precocious puberty (CPP), which is mediated
, y1 S2 C6 H7 H& e" Q: ^: ythrough the hypothalamic pituitary gonadal axis, has( f8 x* ]8 q" X5 {/ P r
a higher incidence of organic central nervous system
* x; J. l! C2 p' }, i% v6 qlesions in boys.1,2 Virilization in boys, as manifested
; `, C# [2 R' d- Cby enlargement of the penis, development of pubic
" ?- d$ l1 X) g2 ` Chair, and facial acne without enlargement of testi-
2 z. f# u+ Q* u3 @cles, suggests peripheral or pseudopuberty.1-3 We
% e5 ~( g4 d Z% T* X! mreport a 16-month-old boy who presented with the
# P4 ^5 Q: x. }. H* P) W8 Penlargement of the phallus and pubic hair develop-- Q" ~, q( a% A C4 @* [" i* [- }
ment without testicular enlargement, which was due
9 |1 |: [2 y) Rto the unintentional exposure to androgen gel used by# r% T+ k! F- N7 H, c$ Y
the father. The family initially concealed this infor-
9 X( y$ g1 ?& }4 `4 _* u5 imation, resulting in an extensive work-up for this
& A, R, T; P- q7 {child. Given the widespread and easy availability of7 j5 x! h) F/ c8 {! o W$ u
testosterone gel and cream, we believe this is proba-
- t" M; ?) D0 f% Ebly more common than the rare case report in the, a1 |6 u' w2 h) S9 Y
literature.4
' M; Q. r5 t& _" a3 }/ ?% ?Patient Report
- D a( j) T9 z$ N5 B& f; |; CA 16-month-old white child was referred to the
* `0 M1 ~ v6 b" A5 {endocrine clinic by his pediatrician with the concern
\0 B7 A7 x9 c3 o& v, g8 bof early sexual development. His mother noticed/ K: A/ n# l8 d/ ?: i. g
light colored pubic hair development when he was
' s3 S, d, W5 N3 ~' i( z9 mFrom the 1Division of Pediatric Endocrinology, 2University of
* q$ |% U/ o y+ tSouth Alabama Medical Center, Mobile, Alabama.
% u! h; _- K+ [& I" N2 @Address correspondence to: Samar K. Bhowmick, MD, FACE, X% K0 [( S& c/ M+ N( e
Professor of Pediatrics, University of South Alabama, College of
! s$ L* Z2 x0 f# V9 @% f. MMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;: ]) k- }9 _7 w3 ?, n5 t; ~
e-mail: [email protected].( ?2 O* J( }' U
about 6 to 7 months old, which progressively became
4 {) z: N: i# N* ~) ddarker. She was also concerned about the enlarge-
, ?& U6 x( C) J3 Mment of his penis and frequent erections. The child
( ~( i% Z8 {7 K! R: [" |' ]was the product of a full-term normal delivery, with
b. u' F& X- e, {: J ]; pa birth weight of 7 lb 14 oz, and birth length of2 N1 ?: [; }- d' k
20 inches. He was breast-fed throughout the first year) L# N3 y5 Y1 i: ^3 u
of life and was still receiving breast milk along with
" C% h; V* e/ j- u0 Asolid food. He had no hospitalizations or surgery," j) `: E1 U5 M, Y g
and his psychosocial and psychomotor development
7 `% @9 M' _7 ?: G& b) Wwas age appropriate.
/ _& f1 j* P- c. T! D7 X3 JThe family history was remarkable for the father,# j4 ], j# x1 H5 `3 E
who was diagnosed with hypothyroidism at age 16,( n2 _, X* q6 t) H5 H K- ^
which was treated with thyroxine. The father’s
$ _: Q3 h( W4 lheight was 6 feet, and he went through a somewhat
: q" d) `2 i. B% A4 rearly puberty and had stopped growing by age 14.
; q( v) J, F9 K% o3 uThe father denied taking any other medication. The
) ?7 z6 K4 j w% H( g' uchild’s mother was in good health. Her menarche
: E7 K+ R5 L, z- X: u; p! Gwas at 11 years of age, and her height was at 5 feet N2 E/ K1 _% f5 s3 B( V! `# s6 w$ m
5 inches. There was no other family history of pre-
6 {6 m, }+ }2 d6 F. u4 dcocious sexual development in the first-degree rela-
1 ?" u& o$ T: i" E& X* u& Utives. There were no siblings.
8 M8 q$ [2 H* V; u: z W- dPhysical Examination
" @) b% p$ j, w7 wThe physical examination revealed a very active,
" ]9 O9 K) I' w6 F a1 J. Zplayful, and healthy boy. The vital signs documented
) N" ?3 z% n" k: A) Y6 Sa blood pressure of 85/50 mm Hg, his length was! r; p4 I; |( I' p" L
90 cm (>97th percentile), and his weight was 14.4 kg
$ X! d0 z. {! ^% ~! M) l) S# M(also >97th percentile). The observed yearly growth; Q0 b# r4 Q) l, Z$ u
velocity was 30 cm (12 inches). The examination of+ b; b5 o# I w" T$ i
the neck revealed no thyroid enlargement.
( V' S% R& N8 g( b, N5 A7 E! J0 Z4 rThe genitourinary examination was remarkable for& k. I5 E u/ Z4 m3 e. q
enlargement of the penis, with a stretched length of& |; g$ ~/ |4 j
8 cm and a width of 2 cm. The glans penis was very well
! `0 t5 P" H5 G& ldeveloped. The pubic hair was Tanner II, mostly around8 M" b2 d$ { V2 C
540
: |5 P& D; f q" I! P: B. Jat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
" V; a ?) `( d! Qthe base of the phallus and was dark and curled. The7 F" w4 M6 l' l
testicular volume was prepubertal at 2 mL each." a0 J4 K( M: h4 s2 a9 c. Z J
The skin was moist and smooth and somewhat1 y5 Y2 X" p, T
oily. No axillary hair was noted. There were no; S6 l# E$ ~% ~- B2 t* D" B* P
abnormal skin pigmentations or café-au-lait spots.
$ f# a- [# U$ r1 w9 w7 FNeurologic evaluation showed deep tendon reflex 2+ ^) v- I! x& R
bilateral and symmetrical. There was no suggestion; I# l3 ~/ D- Z( x9 v
of papilledema.8 D5 n& E0 D4 p! X+ n& m3 W4 x
Laboratory Evaluation
- t( ?4 E0 ]+ }) {( g6 d) iThe bone age was consistent with 28 months by$ D6 t$ A4 e7 A: @$ m5 l, _
using the standard of Greulich and Pyle at a chrono-
/ m% F! x5 `0 o/ G9 D7 N6 e" Jlogic age of 16 months (advanced).5 Chromosomal
" o' g. z' R, K" o4 n% Gkaryotype was 46XY. The thyroid function test7 e0 V$ L$ u4 l; n7 J
showed a free T4 of 1.69 ng/dL, and thyroid stimu-4 o, q5 T, w( ]" z. u
lating hormone level was 1.3 µIU/mL (both normal).
. e: ~' G% \# ~4 d/ N+ ?* x3 oThe concentrations of serum electrolytes, blood
6 o; q$ _# O5 g, M+ U3 _& K2 X! vurea nitrogen, creatinine, and calcium all were
# V7 c) P6 o3 m- _within normal range for his age. The concentration
" x! ~/ H2 A: mof serum 17-hydroxyprogesterone was 16 ng/dL" T- U1 R. h7 g* ]& I" \' k
(normal, 3 to 90 ng/dL), androstenedione was 20
' I+ {0 Y" h/ V$ C9 ang/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
- a: J# V1 Y+ A, J1 ~9 o- [ @" \terone was 38 ng/dL (normal, 50 to 760 ng/dL),4 o0 A) P% M" z* F0 }
desoxycorticosterone was 4.3 ng/dL (normal, 7 to; P' d* Z( R( N$ Z
49ng/dL), 11-desoxycortisol (specific compound S)
; R; m% o( I& ~0 M3 pwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-, @' K J. U& x/ y" I
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total# q- u3 Q& W: s/ [
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
( `6 K: u! D' ` ]+ Qand β-human chorionic gonadotropin was less than
5 ]1 Y9 D; r" z6 ?3 ]5 mIU/mL (normal <5 mIU/mL). Serum follicular6 F1 w0 Z& W( b0 z3 }! G
stimulating hormone and leuteinizing hormone" d, ]/ W0 \ K
concentrations were less than 0.05 mIU/mL
/ M0 Z+ V$ B* k! V* q" W(prepubertal).
- J1 u( j% ~2 S* A1 eThe parents were notified about the laboratory
# J4 d/ f" y8 \# Z! I$ z8 Q4 tresults and were informed that all of the tests were
/ ^, Z: \; Z- }normal except the testosterone level was high. The% c! `( z- p0 K0 L
follow-up visit was arranged within a few weeks to
5 e) I$ ]1 Q+ c9 O8 F6 \. gobtain testicular and abdominal sonograms; how-
7 D6 M% c5 u1 o" u9 g3 b& M$ Eever, the family did not return for 4 months.
4 ?, A) N/ [7 d! G/ h& m+ I; a, w, aPhysical examination at this time revealed that the; @. S- P. `: o
child had grown 2.5 cm in 4 months and had gained
5 e) S. M ]" k5 k8 T2 kg of weight. Physical examination remained8 z+ k, U4 n+ z7 ~+ z
unchanged. Surprisingly, the pubic hair almost com-9 g! G+ }/ H$ ?( F6 j: V) l
pletely disappeared except for a few vellous hairs at
; Y; b( e# k, i$ J8 Pthe base of the phallus. Testicular volume was still 2: C, K) b1 h& m
mL, and the size of the penis remained unchanged.$ w2 p) r, c$ {$ q' S
The mother also said that the boy was no longer hav-
6 U0 g! t R7 h1 }% Z; Wing frequent erections.* G; R' v5 a! c$ x6 G
Both parents were again questioned about use of. X% R0 P' W/ n7 m& ?3 \5 F
any ointment/creams that they may have applied to
4 E' t, w6 x& s7 _! N3 a6 N, K# s# ]& J1 ethe child’s skin. This time the father admitted the8 R9 n7 ?; c1 q) Y5 }- p" K+ N
Topical Testosterone Exposure / Bhowmick et al 541. r: F# z& S; d2 a$ }' P( @" e
use of testosterone gel twice daily that he was apply-
) k" c% S8 I1 R; |1 Q, L' A1 eing over his own shoulders, chest, and back area for$ B7 X9 e+ O' B: S/ O
a year. The father also revealed he was embarrassed4 D0 N: k* {5 a6 V5 ]. C) X
to disclose that he was using a testosterone gel pre-, I7 j [3 a+ E3 `
scribed by his family physician for decreased libido
0 D+ H# ?- ~5 ?4 `9 Bsecondary to depression.
7 g4 F9 s6 o: j) GThe child slept in the same bed with parents.
3 Y- O! t% B' J+ x$ sThe father would hug the baby and hold him on his
1 J7 z' w! X2 nchest for a considerable period of time, causing sig-
8 ~0 h' w$ f+ |$ s2 pnificant bare skin contact between baby and father.
S. X2 q8 Y* [, f) y; N. d5 CThe father also admitted that after the phone call,+ e8 J4 e' c1 l
when he learned the testosterone level in the baby' \* e& n$ f" v! ^8 }+ ?
was high, he then read the product information% c6 _. d' ^/ D* k4 |! R* W
packet and concluded that it was most likely the rea-, ^2 c8 v" ?: A* d6 \
son for the child’s virilization. At that time, they
5 A9 b5 Q" |1 M' |" f mdecided to put the baby in a separate bed, and the3 }- r/ a/ d+ W0 H
father was not hugging him with bare skin and had
) q; @; k [ \! E$ n2 C, [been using protective clothing. A repeat testosterone
& s H R* Q1 ]4 P3 `6 g. otest was ordered, but the family did not go to the
0 ~5 `4 a6 w3 n' u4 C: U* m# ~laboratory to obtain the test.4 l# {. l* R4 D" Z5 Z! H {
Discussion) n( t- x3 s; U# s- |
Precocious puberty in boys is defined as secondary( ^0 T) i3 M. G0 O/ n7 U( D) Z
sexual development before 9 years of age.1,46 z3 S0 ?* M) a" g) W
Precocious puberty is termed as central (true) when5 B8 d6 E. [' N. w; n5 r$ O$ B' E; n
it is caused by the premature activation of hypo-( Q6 X- y4 k! V+ i1 ]
thalamic pituitary gonadal axis. CPP is more com-
) `4 l, X/ i' u$ ]2 x9 d; O7 f3 D( n7 u8 Nmon in girls than in boys.1,3 Most boys with CPP
) u4 F3 ?* G( a2 T8 L2 P, }1 I- V; H$ \may have a central nervous system lesion that is
+ z7 ~+ f; ?3 P& F( Nresponsible for the early activation of the hypothal-
6 C9 ~, |8 C) J V& v$ G1 Mamic pituitary gonadal axis.1-3 Thus, greater empha-
6 s& w6 X, J0 w% Rsis has been given to neuroradiologic imaging in
: j) u$ c" x) [6 K9 \5 Zboys with precocious puberty. In addition to viril-, Q! @ o) v! t D" J x
ization, the clinical hallmark of CPP is the symmet-
' z- \! U! n9 h4 trical testicular growth secondary to stimulation by3 D# n! U# H9 g- S
gonadotropins.1,3
7 I& n+ B" G: b7 o0 DGonadotropin-independent peripheral preco-/ O) X7 c( N/ p7 d7 N
cious puberty in boys also results from inappropriate4 V; x: R: K7 U% |9 V+ B$ v: ^7 S
androgenic stimulation from either endogenous or& |) V7 t# S' x+ A
exogenous sources, nonpituitary gonadotropin stim-& D5 t: V. e. p4 T" V& V9 ^, s
ulation, and rare activating mutations.3 Virilizing& Q/ [) n5 k3 G
congenital adrenal hyperplasia producing excessive
' e* Z; G3 a4 o" b, e/ t% `adrenal androgens is a common cause of precocious
a" a; S- [& P$ V1 h- {, rpuberty in boys.3,4
. b0 @& U0 F0 u* N' W6 Y' bThe most common form of congenital adrenal
A( J3 J2 x* o! w; f- }+ Ohyperplasia is the 21-hydroxylase enzyme deficiency.4 y& A. Q& D7 b# H N
The 11-β hydroxylase deficiency may also result in
3 [# \, D9 z" D$ pexcessive adrenal androgen production, and rarely,* Z, i4 }' w3 v0 A5 \
an adrenal tumor may also cause adrenal androgen
8 Q* S) Q# F7 lexcess.1,3
* i: o" B& P1 q, d( a8 Bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ I9 q& Q1 n7 H0 T
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
( Y! j9 ]9 L; FA unique entity of male-limited gonadotropin-5 i* U, R* w) i) f3 S8 s5 S/ H" j
independent precocious puberty, which is also known2 v v1 Y" w0 j: M, p; i
as testotoxicosis, may cause precocious puberty at a- I3 K" a' h0 |$ O; m7 J! u
very young age. The physical findings in these boys7 c& \9 D" i+ @& ^, u$ `) u6 \2 Z
with this disorder are full pubertal development,
4 y# i8 d% k; p0 Yincluding bilateral testicular growth, similar to boys
* Z( ^5 {2 d# T4 Pwith CPP. The gonadotropin levels in this disorder2 r' _5 [+ X/ x& y5 F4 b
are suppressed to prepubertal levels and do not show
! _( D4 q- S( P8 Bpubertal response of gonadotropin after gonadotropin-/ B0 | [& K3 B4 W9 s$ h' b0 i! x
releasing hormone stimulation. This is a sex-linked
! ~& U/ s8 m) x+ cautosomal dominant disorder that affects only
- p) T* X: _- W; N( V- Wmales; therefore, other male members of the family
5 N A0 L( T8 a7 T+ dmay have similar precocious puberty.3
' R8 K8 L: g# p$ EIn our patient, physical examination was incon-5 Z& ]- z6 i4 a8 J
sistent with true precocious puberty since his testi-
1 X/ X# d8 `% Q7 c6 S' i; fcles were prepubertal in size. However, testotoxicosis
% B R- u) c& [' {2 F4 Q! B2 a0 kwas in the differential diagnosis because his father
4 V' N3 C0 G; i3 u4 e& Rstarted puberty somewhat early, and occasionally,
& N7 L% s6 O" a* ?testicular enlargement is not that evident in the
' V3 u3 p7 X5 E* Gbeginning of this process.1 In the absence of a neg-5 z7 o" ^+ [7 P7 y5 A+ X
ative initial history of androgen exposure, our O: G; s7 i' Q. D! P
biggest concern was virilizing adrenal hyperplasia,' E3 N5 E) u5 T0 n) j( e7 Z8 v3 C! S
either 21-hydroxylase deficiency or 11-β hydroxylase
. }5 ?9 j5 V! U3 r' }! bdeficiency. Those diagnoses were excluded by find-
, c5 F0 _' [0 m, c' R1 y: Ning the normal level of adrenal steroids.* D& V! X+ Z" D% v: X
The diagnosis of exogenous androgens was strongly
9 D/ T4 ?" z+ E* ?& Isuspected in a follow-up visit after 4 months because: C. F4 ~3 n! d9 C! @
the physical examination revealed the complete disap-
3 q0 O1 o) `8 B* f8 ~" Q6 J0 z# j3 s% Tpearance of pubic hair, normal growth velocity, and
8 z4 L0 E* Q9 _decreased erections. The father admitted using a testos-
4 {, R o; K9 Yterone gel, which he concealed at first visit. He was
" T X5 J1 @4 Z4 T" [using it rather frequently, twice a day. The Physicians’
( v. U" ]# m5 B/ h) ^2 C- F9 \# fDesk Reference, or package insert of this product, gel or* v2 ^1 U3 Y3 ~
cream, cautions about dermal testosterone transfer to; ~$ k$ x, e7 D: c! ^
unprotected females through direct skin exposure.- z; u7 g" S2 h' D% Q Q0 y
Serum testosterone level was found to be 2 times the
& b" S7 ?; S$ Fbaseline value in those females who were exposed to
1 |; S& C; P2 B3 t( P7 Beven 15 minutes of direct skin contact with their male4 P N% S. J$ A
partners.6 However, when a shirt covered the applica-
1 w2 h* x: D% o' Etion site, this testosterone transfer was prevented.; r7 w5 z/ H- p% S1 D
Our patient’s testosterone level was 60 ng/mL,
) X/ M4 x R1 {" |which was clearly high. Some studies suggest that
3 f( w& X4 d! @$ R2 gdermal conversion of testosterone to dihydrotestos-
8 A7 y- {5 J4 j1 ^: gterone, which is a more potent metabolite, is more
( S& ~8 l. Z' ]1 Eactive in young children exposed to testosterone
2 e4 r5 S3 c: }exogenously7; however, we did not measure a dihy-/ A9 v) z4 q! r- c; V+ T
drotestosterone level in our patient. In addition to
8 `3 H d9 T6 {5 ~/ ?* ^virilization, exposure to exogenous testosterone in
% C1 S" |0 Z# `, r0 mchildren results in an increase in growth velocity and
* H$ f' U( R; N3 z1 D1 P. hadvanced bone age, as seen in our patient.$ u& ]) w9 {* v; [
The long-term effect of androgen exposure during
0 U5 r5 K- v `/ E+ @+ Yearly childhood on pubertal development and final
5 T- o& C8 v. w' t( Ladult height are not fully known and always remain. d8 w* ?6 S5 x0 j: j& J
a concern. Children treated with short-term testos-' x+ p$ a2 [3 ^) I+ s
terone injection or topical androgen may exhibit some
- O6 b0 B2 x3 W% eacceleration of the skeletal maturation; however, after, C4 G4 r& F# C w
cessation of treatment, the rate of bone maturation0 p' H" f7 j% A# a3 c
decelerates and gradually returns to normal.8,9
2 A, t0 l" w4 d* O2 n3 S8 a. M: O+ iThere are conflicting reports and controversy" J6 o* g8 Q* A
over the effect of early androgen exposure on adult( z1 n' ?# W; B
penile length.10,11 Some reports suggest subnormal3 i" [- _' i0 ~6 Q, h
adult penile length, apparently because of downreg- U: ]. L3 f3 z, O% ~
ulation of androgen receptor number.10,12 However,
( C$ f$ Y# S! w# KSutherland et al13 did not find a correlation between, [, U+ [- H7 c: A) k' T4 |: z
childhood testosterone exposure and reduced adult
( r- o8 e4 R) E# Openile length in clinical studies.
/ Z) i1 P% W4 t( [Nonetheless, we do not believe our patient is9 E, l9 \/ R. l1 p9 a% c) t$ d
going to experience any of the untoward effects from
/ f, L% [1 `+ F7 f9 u. Gtestosterone exposure as mentioned earlier because# w0 i7 ^* T* L( V9 i
the exposure was not for a prolonged period of time.
- y& |" g; c& W! x( T* I5 BAlthough the bone age was advanced at the time of
! a% V2 j* p, R+ ]' S! ^diagnosis, the child had a normal growth velocity at+ L! B+ @2 U; d* j
the follow-up visit. It is hoped that his final adult
* L5 s' D' R" [; qheight will not be affected.
) X, Y5 B+ a1 ~) `Although rarely reported, the widespread avail-8 v( ~1 ^: n" e0 F7 l0 h a) I& Q
ability of androgen products in our society may! P' h/ j2 C$ b( x w3 L
indeed cause more virilization in male or female# y* R$ k6 E ~% O' M, E2 A. o
children than one would realize. Exposure to andro-4 ]5 p+ H+ o- }& W, D! t, x$ Y
gen products must be considered and specific ques-
- v# l) E+ g s, p+ Mtioning about the use of a testosterone product or
`! e% W* A" b) s+ g7 igel should be asked of the family members during
/ ~' \3 K4 x# P) ]& N1 @the evaluation of any children who present with vir-7 {4 U: q) o6 ^& J) J4 H9 V( @( L
ilization or peripheral precocious puberty. The diag-2 O4 m0 h7 R& h; J9 b, T
nosis can be established by just a few tests and by
. a/ x8 ^" O2 U- ~appropriate history. The inability to obtain such a
+ {1 b( ^" D. B/ d3 W5 x$ B' ~) Xhistory, or failure to ask the specific questions, may/ ?- j8 f: B) k5 i6 _+ {6 i V: k
result in extensive, unnecessary, and expensive
" h$ u& q* f7 I! Minvestigation. The primary care physician should be$ I4 l( t* J& j8 {4 V; J7 G: E' V
aware of this fact, because most of these children; J4 [# e1 t' U9 {0 [+ r
may initially present in their practice. The Physicians’+ B2 z) P# U) w6 `# g9 e8 G' o
Desk Reference and package insert should also put a
' w \3 N. [+ W! S1 h7 rwarning about the virilizing effect on a male or2 h& A( z- ?- f8 j7 @, Q6 v
female child who might come in contact with some-
2 Q1 B: f- i0 _7 u Hone using any of these products.
% L9 e5 v. |2 @References
0 U+ x- A) Y( O! V, y1 N1. Styne DM. The testes: disorder of sexual differentiation4 {8 @& j9 w" M
and puberty in the male. In: Sperling MA, ed. Pediatric
, x6 \: Q0 o( b- cEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
9 W; h% N, ~% d9 y4 ^2002: 565-628.
- U! u, m' S( ]2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
% H) l* y0 m2 } F1 K( k* ipuberty in children with tumours of the suprasellar pineal |
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