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Sexual Precocity in a 16-Month-Old
& l' @' |6 e8 c6 @% E, i% \2 [Boy Induced by Indirect Topical6 [$ _: ]" Z2 s
Exposure to Testosterone# @( u( T. ^0 T: R. S3 R
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2 C$ @0 R, C# o: z I
and Kenneth R. Rettig, MD11 j" a$ H( I' ~% S* d
Clinical Pediatrics- V: J i; ~* R7 v3 g5 Z5 _
Volume 46 Number 69 j v$ [- N" x# K
July 2007 540-543
3 `! q( x# j5 Y$ X( p$ I4 y$ B* i© 2007 Sage Publications5 r0 f0 {7 g0 y' B; P& X7 N" g
10.1177/0009922806296651
5 G# l1 }' t5 [! h$ Hhttp://clp.sagepub.com
( I. j+ X4 U/ ?3 L2 ~+ ]hosted at; O( o2 ?. e& Y: m: c8 n# a
http://online.sagepub.com; n' R, o0 U% ~
Precocious puberty in boys, central or peripheral,$ U0 {0 G. O- y1 x( g& i
is a significant concern for physicians. Central
, D6 _3 J* C Z$ V1 r# D+ Z Sprecocious puberty (CPP), which is mediated7 g" M! u. {2 L: T( \$ ^) M
through the hypothalamic pituitary gonadal axis, has9 m1 h9 D& O9 d
a higher incidence of organic central nervous system
" M# k- C3 p. a. L) S3 |3 [lesions in boys.1,2 Virilization in boys, as manifested
& R- H) l/ Z _by enlargement of the penis, development of pubic
8 }- L6 m6 r/ v: n- [2 M g1 vhair, and facial acne without enlargement of testi-7 |' _/ l R1 p6 l$ L3 {) E
cles, suggests peripheral or pseudopuberty.1-3 We
6 T6 G; m: K" g. T* A. c5 o1 ]% |report a 16-month-old boy who presented with the8 ^) w! m& A9 [5 d! F' Z, p7 f S
enlargement of the phallus and pubic hair develop-2 T8 Q% x9 s) M& ?5 x. j
ment without testicular enlargement, which was due
9 J+ ~8 J# ~9 G- a- nto the unintentional exposure to androgen gel used by
2 x& l, C" c: h% rthe father. The family initially concealed this infor-: O5 D5 o! Z+ I& ^$ |
mation, resulting in an extensive work-up for this
, _, F: ~5 }' M( T$ Bchild. Given the widespread and easy availability of
, _* k* n* A" p$ v$ z2 f) Otestosterone gel and cream, we believe this is proba-# Y. F: v, _+ B1 ?6 |8 G
bly more common than the rare case report in the
& n9 U3 f2 x' w, Yliterature.4* w: }, p# `0 k) a0 c' n! g
Patient Report
" u5 t7 l9 X1 L# ]1 {A 16-month-old white child was referred to the
" S0 j+ H! J$ G& Iendocrine clinic by his pediatrician with the concern; T9 E1 q# k9 Y7 h5 c# P/ Q
of early sexual development. His mother noticed
/ U" T( |* I: e: ]light colored pubic hair development when he was7 I6 @& q! Y; G+ U
From the 1Division of Pediatric Endocrinology, 2University of$ E0 [. Z+ B5 y0 J5 G8 b; M# t
South Alabama Medical Center, Mobile, Alabama.7 R* I2 z) i# \4 m$ s
Address correspondence to: Samar K. Bhowmick, MD, FACE,
\3 H9 w8 T4 I0 m* f5 K: a+ K+ e& q3 ?Professor of Pediatrics, University of South Alabama, College of
$ j* J" h( t0 o- t$ _4 R- @Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
1 q9 R- b8 J* Q, W' r" me-mail: [email protected].
# u7 _1 E0 Q/ r+ Fabout 6 to 7 months old, which progressively became
7 z, y. \! p. J$ O6 f& M5 t0 |darker. She was also concerned about the enlarge-
$ }: p" [8 A ^. p' _4 Y& fment of his penis and frequent erections. The child) z; g+ K$ C# `) N; b
was the product of a full-term normal delivery, with5 A4 Q* b% T2 ?* x3 T- V
a birth weight of 7 lb 14 oz, and birth length of6 S4 k0 u5 [4 w) H
20 inches. He was breast-fed throughout the first year
" y$ N+ L2 G2 H: j1 dof life and was still receiving breast milk along with1 m0 G" J; x$ x0 \1 }3 x. Y: m8 Y
solid food. He had no hospitalizations or surgery,$ _) F% p- {! S+ ~* j: P6 `0 b
and his psychosocial and psychomotor development
; p# t; r+ p: j4 f e1 G! `/ Iwas age appropriate.
+ K+ ?& @5 l$ n2 P; YThe family history was remarkable for the father,; l- E/ z1 \8 @/ ^
who was diagnosed with hypothyroidism at age 16, K3 r# H. Y) _& \ d
which was treated with thyroxine. The father’s
# ^1 v6 t9 T" P2 }' }4 p+ qheight was 6 feet, and he went through a somewhat, g" x' P# S& h/ x
early puberty and had stopped growing by age 14. h8 P- ]1 o$ q' m( z9 F
The father denied taking any other medication. The
$ K" ]4 {* t/ Z# O# d+ ]) |. Cchild’s mother was in good health. Her menarche
' l$ }7 p: c4 R; i( s L4 b. awas at 11 years of age, and her height was at 5 feet3 F1 d. j/ S' e, G
5 inches. There was no other family history of pre-! x4 Z( M7 ^' |
cocious sexual development in the first-degree rela-
/ b+ s% i, H, `2 e$ q3 i8 Utives. There were no siblings.
7 G; \# y8 `# SPhysical Examination
8 e5 g" c6 q- q# q3 {The physical examination revealed a very active,
$ o/ w# ^+ v" { z& uplayful, and healthy boy. The vital signs documented x# k) Y. u( f G
a blood pressure of 85/50 mm Hg, his length was
, H) H/ f2 t) m; ~) \90 cm (>97th percentile), and his weight was 14.4 kg
, i6 B* N9 x: l" R0 |(also >97th percentile). The observed yearly growth% L4 n" [" Y7 V' p: v2 j
velocity was 30 cm (12 inches). The examination of
' D9 t0 e! a/ K% i$ xthe neck revealed no thyroid enlargement.
# s/ c- d# Q& X& rThe genitourinary examination was remarkable for/ D" E4 R) Z% ^& b/ I( x
enlargement of the penis, with a stretched length of
: I Z" x, z3 ^( `; e8 cm and a width of 2 cm. The glans penis was very well
5 }( q8 K: S7 _. [$ pdeveloped. The pubic hair was Tanner II, mostly around e2 o( |$ I- o+ [0 E
540' f1 T! G2 y6 T) ]6 ^9 n
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: _) _9 a7 v2 E" H# bthe base of the phallus and was dark and curled. The
) c0 t, O! |: ttesticular volume was prepubertal at 2 mL each.
7 `% `1 U4 P( S, |" x6 I; fThe skin was moist and smooth and somewhat
. _9 O9 E! A s- `' m4 F! O8 l% ~& a. Voily. No axillary hair was noted. There were no+ ^, c. i/ c9 M0 P; e7 U, W) X
abnormal skin pigmentations or café-au-lait spots.
8 [2 V+ [. W$ b) h% _. t( mNeurologic evaluation showed deep tendon reflex 2+. j$ L; x+ z' \% r5 s7 u
bilateral and symmetrical. There was no suggestion: r( n' e4 I( p0 {4 b/ O6 ]
of papilledema.0 W2 d! V7 @! U: h2 v5 i
Laboratory Evaluation* L/ {" Z7 |# ?* R
The bone age was consistent with 28 months by2 l! t/ R# S/ a" ?. Z
using the standard of Greulich and Pyle at a chrono-, g( u1 v( r. N, Q5 |8 O
logic age of 16 months (advanced).5 Chromosomal
0 m; h1 n/ a3 `" u. _/ g7 Dkaryotype was 46XY. The thyroid function test, O1 p% R n* G7 G5 @* L3 t
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
% Q# v' `2 _( G; F! L8 Q+ T: ilating hormone level was 1.3 µIU/mL (both normal).
9 D; G$ K7 _7 @; t1 y! t; X; GThe concentrations of serum electrolytes, blood! E% P, i$ z4 y- S/ d3 Q. C; Z
urea nitrogen, creatinine, and calcium all were7 J: t1 r. h' ~# V: g
within normal range for his age. The concentration
: m- U- U6 k4 {- Dof serum 17-hydroxyprogesterone was 16 ng/dL
; M8 G3 ]& O+ ~. y6 n( O o! G(normal, 3 to 90 ng/dL), androstenedione was 20
+ [3 j1 f* V" j `7 cng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
3 j! W4 l i9 D1 s( C2 bterone was 38 ng/dL (normal, 50 to 760 ng/dL),, v3 ~; ^2 m; b- k6 V
desoxycorticosterone was 4.3 ng/dL (normal, 7 to, W- B7 A9 w, t0 D4 U l
49ng/dL), 11-desoxycortisol (specific compound S)
* v0 z( C7 i7 Fwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
9 L* E. h: @. }8 ltisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* a- ?: d+ j- ~2 C% Rtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),- @2 ~# F4 Z$ ~% f& P8 h$ I
and β-human chorionic gonadotropin was less than, }% p4 y* u& f5 a7 r% k9 w
5 mIU/mL (normal <5 mIU/mL). Serum follicular
+ K- I% E$ u5 c4 Gstimulating hormone and leuteinizing hormone
+ [; t5 G) D: y, _' f% fconcentrations were less than 0.05 mIU/mL8 y y$ F1 c+ l0 l/ j3 g( v' H
(prepubertal).4 m$ e$ C3 i5 U1 K
The parents were notified about the laboratory) ^: b5 \! v' y3 |
results and were informed that all of the tests were
# {+ q& l0 q% q( ~5 Enormal except the testosterone level was high. The% |) h$ M' k7 E F! u
follow-up visit was arranged within a few weeks to. z, e( c* S& S2 y
obtain testicular and abdominal sonograms; how-
/ d( T, v! A' u X! u+ ^. Xever, the family did not return for 4 months.7 \, z( B, @# n: s1 B0 w
Physical examination at this time revealed that the
$ v5 ~( O8 {' }: h2 \ e! y, X! A/ ichild had grown 2.5 cm in 4 months and had gained
' n9 ]8 B! {5 x" g; H( H- L2 kg of weight. Physical examination remained# l# L) W( x) W/ N7 t, c) r5 w7 L
unchanged. Surprisingly, the pubic hair almost com-1 P# U' _3 q9 m
pletely disappeared except for a few vellous hairs at3 V) h. k- e* E( X% i7 I
the base of the phallus. Testicular volume was still 2" m$ M- |4 K. z* T' s
mL, and the size of the penis remained unchanged.
9 a- x* {3 @; b2 NThe mother also said that the boy was no longer hav-4 [2 l/ L2 O- q' q/ Y6 j
ing frequent erections.7 o! M: H. H. R2 M& W- {' R0 f
Both parents were again questioned about use of
. Y6 ~% }5 X' m9 b5 ^any ointment/creams that they may have applied to
9 ~' l! D6 M+ O/ Athe child’s skin. This time the father admitted the
' T2 ?0 E1 Q/ ATopical Testosterone Exposure / Bhowmick et al 541% O5 t* N0 O; y) j+ p: J
use of testosterone gel twice daily that he was apply-# l! U2 G4 E# \3 d5 [
ing over his own shoulders, chest, and back area for
" v6 N! V u; C" Ea year. The father also revealed he was embarrassed
% G) a! P' N9 Y1 V, Z3 N4 fto disclose that he was using a testosterone gel pre-
8 m# c' ~+ \: \% C9 Y" Fscribed by his family physician for decreased libido
0 ^: u: I8 f$ P0 tsecondary to depression.5 W; j" i5 D' X9 V
The child slept in the same bed with parents.
) ?( a( C' ^# B$ lThe father would hug the baby and hold him on his
- _8 g; f( ]4 {' y" Z- m0 uchest for a considerable period of time, causing sig-& E6 Y2 i1 ~7 b; u* G2 h- A7 K
nificant bare skin contact between baby and father.
/ L! l" `& {$ @2 oThe father also admitted that after the phone call,5 \: q. V8 v: T5 `- A# A1 t% N
when he learned the testosterone level in the baby
e1 H& C7 p" T4 L+ o) H0 Cwas high, he then read the product information6 F9 F, ^) R, n3 Z' N a
packet and concluded that it was most likely the rea-, H, K. b7 h0 `
son for the child’s virilization. At that time, they
( r' |0 P8 [! j v: bdecided to put the baby in a separate bed, and the/ x, B) ]( K x7 |0 q N
father was not hugging him with bare skin and had
# y9 W+ S: f8 N; T; ]been using protective clothing. A repeat testosterone
2 |* B$ B: ]. j, B. |test was ordered, but the family did not go to the
6 C- R% b X( M3 B9 i2 `$ plaboratory to obtain the test.5 l. B, c3 f" C0 Q1 _
Discussion) l9 E8 O: z* J4 r$ ^0 \
Precocious puberty in boys is defined as secondary
9 |3 R7 j7 N% B# d6 Gsexual development before 9 years of age.1,43 y8 ?# A2 ~+ \+ V
Precocious puberty is termed as central (true) when
( w$ @7 u S4 qit is caused by the premature activation of hypo-
- b$ x: K/ t' {# N4 i0 fthalamic pituitary gonadal axis. CPP is more com-
" u+ Z# k! }7 w+ _4 o; E9 k" Qmon in girls than in boys.1,3 Most boys with CPP6 U- y+ A+ j$ x+ ]
may have a central nervous system lesion that is7 T; M. T4 h0 F- Q" t6 Y0 o4 C
responsible for the early activation of the hypothal-" ~0 S4 y4 {. S. c$ Z D1 H8 J
amic pituitary gonadal axis.1-3 Thus, greater empha-
" Q" E0 Z+ _' gsis has been given to neuroradiologic imaging in
1 \7 h5 g! x5 q. L1 i: Mboys with precocious puberty. In addition to viril-
0 z* e7 D* N, k4 }ization, the clinical hallmark of CPP is the symmet-
' ?; [5 p! V/ e! f5 |6 M/ _8 S3 {- srical testicular growth secondary to stimulation by
% [. k9 z0 w7 |6 @8 @) Ygonadotropins.1,3
$ t7 U8 v$ K7 ]2 b/ P3 b! c% iGonadotropin-independent peripheral preco-
: z* z. V' S. ]- pcious puberty in boys also results from inappropriate6 [! s! Y" R% B2 Z; j
androgenic stimulation from either endogenous or
. j. _% |3 K+ Z. g* A+ c/ k9 w8 Y. aexogenous sources, nonpituitary gonadotropin stim-
# T. e2 w2 u" k6 L" p5 Julation, and rare activating mutations.3 Virilizing+ z5 q/ Z6 u! _5 R1 K" p
congenital adrenal hyperplasia producing excessive
) R5 o( g* Z8 `adrenal androgens is a common cause of precocious% k* D6 d4 |7 K2 |
puberty in boys.3,4
0 ?* b' C3 P9 _# k/ ]/ P n! jThe most common form of congenital adrenal
3 W# E4 U0 X, G& qhyperplasia is the 21-hydroxylase enzyme deficiency.
+ |3 G( W% q, ]The 11-β hydroxylase deficiency may also result in
3 N9 H& ~ o: M. b1 }% q7 T1 rexcessive adrenal androgen production, and rarely,, Z- d$ ^5 A/ _3 v( K% U9 p& L5 c
an adrenal tumor may also cause adrenal androgen/ T, O; }: I3 k" W: r
excess.1,3
1 B$ n& ?( N4 i) |5 fat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
: t n. N p. i' B9 G( P542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
0 |; Z% {2 E TA unique entity of male-limited gonadotropin-
9 z7 i% H7 P7 ]2 O* f7 [- Vindependent precocious puberty, which is also known; X, `, {) x5 l F; _
as testotoxicosis, may cause precocious puberty at a
9 Q3 Q) e) j7 dvery young age. The physical findings in these boys8 o# C9 E! P& Q) L, A9 l+ D
with this disorder are full pubertal development,
$ V' a. r+ x$ m9 D5 |including bilateral testicular growth, similar to boys
+ @3 r! G. Z5 U1 y* i0 p" m uwith CPP. The gonadotropin levels in this disorder' Z5 l" A8 o: l n1 C7 t
are suppressed to prepubertal levels and do not show
! }1 v7 R" ]( E! s$ u0 v6 ?pubertal response of gonadotropin after gonadotropin-$ }3 M" g* _5 F/ o) {
releasing hormone stimulation. This is a sex-linked
A3 j4 |1 P( C u1 g1 h! x/ q; ^autosomal dominant disorder that affects only
3 e" H6 M9 p" O7 g) w4 kmales; therefore, other male members of the family
) j9 z( |, F) L! jmay have similar precocious puberty.3% f+ d. y6 h) R
In our patient, physical examination was incon- g- b( b5 [4 M8 B2 M. h6 D, A
sistent with true precocious puberty since his testi-
, }( O6 m# } C: |4 A4 i$ y, Ncles were prepubertal in size. However, testotoxicosis
/ c1 r2 ]9 @8 \' \was in the differential diagnosis because his father
4 V' Z& u/ q) f! `started puberty somewhat early, and occasionally,
9 Q' u5 J& p1 u1 O1 ]5 q: o# P$ btesticular enlargement is not that evident in the/ ~& ^# ]/ A; v4 `6 \) _' |
beginning of this process.1 In the absence of a neg-% Q+ A$ k0 n3 V; _# W q% Z2 q
ative initial history of androgen exposure, our
8 l3 u0 [" y9 j0 V" g5 Y; R pbiggest concern was virilizing adrenal hyperplasia,' y5 t5 ~6 b+ ~% B% R$ p/ q
either 21-hydroxylase deficiency or 11-β hydroxylase
. ^& W% u6 `$ U% N' mdeficiency. Those diagnoses were excluded by find-
2 D6 @: i7 ]+ _: K; s/ L) \ing the normal level of adrenal steroids.3 m! M7 h: ?4 n& l4 F
The diagnosis of exogenous androgens was strongly
! z9 ?/ @. \- i3 n7 x6 Dsuspected in a follow-up visit after 4 months because# o$ S$ ]& ~4 V2 F' f6 n% w
the physical examination revealed the complete disap-3 J( H- y6 O3 T4 Y2 l1 _+ {
pearance of pubic hair, normal growth velocity, and4 K* V. E0 i2 @/ R. r" [" r
decreased erections. The father admitted using a testos-
6 T" _. P! H, bterone gel, which he concealed at first visit. He was
) ^3 A# Q/ j& v! N1 O" iusing it rather frequently, twice a day. The Physicians’
9 J c! {$ K" a. Z# Q& P# |Desk Reference, or package insert of this product, gel or' }5 H4 u9 L! Y" f. l# C4 O' A
cream, cautions about dermal testosterone transfer to
6 T. e1 ^' } t- z" \9 qunprotected females through direct skin exposure.! q) c+ q9 Y2 j
Serum testosterone level was found to be 2 times the
4 z! @' ^0 h6 o& J' w& g/ _baseline value in those females who were exposed to# U0 P( [, d( ~% ?% h
even 15 minutes of direct skin contact with their male2 y/ h$ p+ {4 P. h
partners.6 However, when a shirt covered the applica-. @9 ^. R1 W A# s6 ~0 J
tion site, this testosterone transfer was prevented.- q. `, T0 `& f+ v
Our patient’s testosterone level was 60 ng/mL,2 t$ n; S+ R, G
which was clearly high. Some studies suggest that
" k4 l9 B# ?6 B3 F1 \% idermal conversion of testosterone to dihydrotestos-4 W, L7 f+ k; X C. G
terone, which is a more potent metabolite, is more
! u0 d. ~5 i. e7 a3 ?! iactive in young children exposed to testosterone
1 [4 ]6 B* E4 E3 H/ m! S# S' Texogenously7; however, we did not measure a dihy-( Q) r3 [$ B& m4 J& P$ L0 M8 X- T
drotestosterone level in our patient. In addition to' A! ~, ^$ Z4 H8 a d
virilization, exposure to exogenous testosterone in; G& {1 [( k: N, i2 H8 l& q
children results in an increase in growth velocity and
9 j) |0 ^( c; `9 Gadvanced bone age, as seen in our patient.
, f. N- y7 G$ I4 \The long-term effect of androgen exposure during
. C W9 D2 V0 Q2 nearly childhood on pubertal development and final4 L# g0 I5 H) W2 {3 B" b
adult height are not fully known and always remain
7 i. Z; A' X: g) X. ta concern. Children treated with short-term testos-4 _0 g7 a/ }6 ]3 W* L" |: G% f7 v
terone injection or topical androgen may exhibit some F- c9 ?$ u0 `' w) C% Q; _4 l2 u
acceleration of the skeletal maturation; however, after
+ J1 O9 Y( z$ g" m5 O; wcessation of treatment, the rate of bone maturation
8 B# V/ N: `: j9 l) a# |decelerates and gradually returns to normal.8,9- @6 D( z" p, ~
There are conflicting reports and controversy+ D# r- I+ ^& @) c& C3 n
over the effect of early androgen exposure on adult
* W) A. w) K6 s& [$ S9 q, ]8 L1 Upenile length.10,11 Some reports suggest subnormal3 z0 H0 o1 G% g, I5 j, N
adult penile length, apparently because of downreg-1 i0 E" R& E: d9 B5 S, e
ulation of androgen receptor number.10,12 However,4 {) V: N; P9 V" I, ]% d
Sutherland et al13 did not find a correlation between
7 S$ J6 S, I" R' Lchildhood testosterone exposure and reduced adult, C2 ` r/ e" S! A
penile length in clinical studies.
$ W+ d8 O+ g$ p0 ]Nonetheless, we do not believe our patient is) i! `: Z1 Z/ {! D2 u( p# o
going to experience any of the untoward effects from$ A4 l' P _6 d9 |2 `5 l
testosterone exposure as mentioned earlier because
# P( p6 }" c/ g# r2 k0 G g. w) [the exposure was not for a prolonged period of time.
* h1 Q' V3 C4 M% N4 zAlthough the bone age was advanced at the time of6 e' z# [: x" V
diagnosis, the child had a normal growth velocity at
( C5 Y- c+ p% m1 Q" i5 |the follow-up visit. It is hoped that his final adult* O4 @! i' _) M2 V
height will not be affected.) e0 E" }- y+ W# i3 u
Although rarely reported, the widespread avail-
& B# g1 {% x7 p* m2 m- ?ability of androgen products in our society may
* _! b9 m! E! K- E4 nindeed cause more virilization in male or female
, X" @ B, `% D( F/ P' a tchildren than one would realize. Exposure to andro-) [! A5 M; k: j0 P4 u5 [, y7 P3 S8 d# ]
gen products must be considered and specific ques-! F1 A+ Q4 a' v/ D6 L. ]
tioning about the use of a testosterone product or
. Y5 m/ A9 b6 A# {gel should be asked of the family members during; n! g6 E8 M- v& z5 J q9 G
the evaluation of any children who present with vir-7 n' v: V; z, @) d! F% a
ilization or peripheral precocious puberty. The diag-
8 S t5 [2 \3 j; `nosis can be established by just a few tests and by
0 h) ^9 p, c* ~+ _2 Qappropriate history. The inability to obtain such a9 o, S5 l4 ^( o8 N7 c, Q
history, or failure to ask the specific questions, may4 }8 n* q: ~; W; |7 N
result in extensive, unnecessary, and expensive
+ b$ ^- m3 v C9 N- V* I7 qinvestigation. The primary care physician should be
, l* I3 w" _4 oaware of this fact, because most of these children+ S2 m9 N5 K4 l, ?# U R E
may initially present in their practice. The Physicians’
$ \' T( Q3 s: U. u, y& bDesk Reference and package insert should also put a; u: [, j' b' m D- z
warning about the virilizing effect on a male or' r- V: s" c2 f: l2 T- X% m
female child who might come in contact with some-
( f. L8 ~" O2 O( A7 f7 @$ ]one using any of these products.
6 L& z& ~5 {+ k: BReferences' N+ r7 s/ b1 Z
1. Styne DM. The testes: disorder of sexual differentiation
, z% g0 t& Q7 |- c# G \/ @ l7 P, Oand puberty in the male. In: Sperling MA, ed. Pediatric
( H3 Y' g* x- ~' ]9 ^0 GEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;: e2 L: D$ L0 I
2002: 565-628.
- {5 {2 O# E9 W) v1 o" H. L2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious* ^( {; n: j" L6 ~ a; L* t
puberty in children with tumours of the suprasellar pineal |
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