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Sexual Precocity in a 16-Month-Old
/ U. J) p% Y( A. ]6 ABoy Induced by Indirect Topical
& K" F1 T1 `4 KExposure to Testosterone. [- G$ P! Q3 `- b5 X0 [
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2! \4 k& L+ _8 O1 I* o+ H% E
and Kenneth R. Rettig, MD1/ r ?' b4 }4 B. `8 ^: y/ O3 }
Clinical Pediatrics
1 p0 ?1 a$ K0 I' j7 Z/ ~1 WVolume 46 Number 6. u1 E$ ?, E+ Y0 y- o3 g6 A
July 2007 540-543
# z- `+ Q) P3 v; b ^& o© 2007 Sage Publications
( K) U) V: O# W8 ?10.1177/0009922806296651
4 H$ D( |/ r1 E; @+ chttp://clp.sagepub.com
7 V) |, H+ ?- {* \; S$ Ihosted at
: q6 N0 B- x- x: M3 Khttp://online.sagepub.com
: o6 ?5 `# ?+ N/ W, }2 U6 {Precocious puberty in boys, central or peripheral,3 B- F. }' s3 l5 u) o
is a significant concern for physicians. Central6 N8 k, R( y" L
precocious puberty (CPP), which is mediated
0 Q( w1 Z# n1 t8 w' L3 pthrough the hypothalamic pituitary gonadal axis, has( p! ^( o9 E% A( O: n E
a higher incidence of organic central nervous system7 a; A3 n: n S9 x* q8 V
lesions in boys.1,2 Virilization in boys, as manifested2 c' r: U) |( U4 [8 ]
by enlargement of the penis, development of pubic. ` G; q3 x& M/ J* z
hair, and facial acne without enlargement of testi-* P+ u/ ~; T8 \) o/ R+ S3 h
cles, suggests peripheral or pseudopuberty.1-3 We. p* V* q/ k+ D& W
report a 16-month-old boy who presented with the
, s0 [( ^# g g' H8 zenlargement of the phallus and pubic hair develop-
9 m9 W0 [( Z' Q: H. Xment without testicular enlargement, which was due
. m4 X- O0 n. kto the unintentional exposure to androgen gel used by
: G: u& J. W# b* w3 B7 C/ mthe father. The family initially concealed this infor-
' I ~& z6 S9 d$ j: Y7 d3 |: ?! @mation, resulting in an extensive work-up for this# o0 v( v2 ^4 G7 X5 D" [
child. Given the widespread and easy availability of
& W$ f. B- i2 ~testosterone gel and cream, we believe this is proba-
; C1 Q+ Q1 T4 Y# c0 Ebly more common than the rare case report in the
9 E; Y1 h! ~8 Y$ T3 J" I3 pliterature.4- J3 f1 h; O4 x4 y1 A
Patient Report
3 G, q% N4 B( E( `A 16-month-old white child was referred to the* x ?. |! O7 k2 g- b# L. a! g9 ]5 d4 ~
endocrine clinic by his pediatrician with the concern
6 t( T2 s7 j6 V, t5 t6 A: m# pof early sexual development. His mother noticed& X. @" I. J% m8 M, `
light colored pubic hair development when he was! Y+ `0 e3 d1 P, P4 X1 i0 B
From the 1Division of Pediatric Endocrinology, 2University of
- u$ T7 p) z4 n' GSouth Alabama Medical Center, Mobile, Alabama.0 O. C' Y+ S/ o
Address correspondence to: Samar K. Bhowmick, MD, FACE,6 Z) J, v9 s: w2 ~+ B' m* I
Professor of Pediatrics, University of South Alabama, College of; N- {" n" k% i( c0 g
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
; Z6 p% W9 {8 Z9 h7 `' |e-mail: [email protected].
0 H, {' z( u- N% Oabout 6 to 7 months old, which progressively became% E+ ?( ?/ c1 a
darker. She was also concerned about the enlarge-4 [3 [3 \) h& h$ F4 V- `! j
ment of his penis and frequent erections. The child
- `5 M- }% \7 H# _; X2 Iwas the product of a full-term normal delivery, with$ z* U7 A' A, L) f9 U( w
a birth weight of 7 lb 14 oz, and birth length of1 @! \- B9 R7 [: D" \ S
20 inches. He was breast-fed throughout the first year, Y) U8 @% l2 w; r: n" x# ~7 f6 C
of life and was still receiving breast milk along with
# v1 s# ` _+ N8 ^solid food. He had no hospitalizations or surgery,
) ?, K0 [$ x f* d L2 _and his psychosocial and psychomotor development
! s7 H/ b* B: G" Zwas age appropriate.; M5 s# A& [" \1 Z
The family history was remarkable for the father,8 P, p. k- e7 ]" b
who was diagnosed with hypothyroidism at age 16,
n( m/ N$ ?' S6 A- c! `which was treated with thyroxine. The father’s1 L; e- O) f2 v' d6 ]
height was 6 feet, and he went through a somewhat! g# l* V! {7 e: Q" D, L3 e4 G8 Z
early puberty and had stopped growing by age 14.
( J( }+ M, t$ i0 NThe father denied taking any other medication. The- s$ ^: o! x. u- T
child’s mother was in good health. Her menarche. S9 }: Y6 r& K% n6 d3 ]+ [
was at 11 years of age, and her height was at 5 feet
& L& A+ y/ Q/ b5 u* {5 inches. There was no other family history of pre-
/ t: }' q O( k. D% a3 c) j; @! m0 `* pcocious sexual development in the first-degree rela-8 c7 F3 j# m) @9 l5 z
tives. There were no siblings.
! ^! n. v& F4 u6 ?6 X wPhysical Examination
' p. F# j: k! _+ y1 K% v) U/ NThe physical examination revealed a very active,
! X; o3 T5 ?0 Wplayful, and healthy boy. The vital signs documented
4 R, i7 S8 L4 W7 @* r3 W, ba blood pressure of 85/50 mm Hg, his length was- z) @! h) p* G
90 cm (>97th percentile), and his weight was 14.4 kg
2 C0 X& i- |) M% g+ k. \(also >97th percentile). The observed yearly growth
& y* a4 R. a! I% W5 A* ovelocity was 30 cm (12 inches). The examination of
3 q" m) F( y" H$ ythe neck revealed no thyroid enlargement.
6 p# d" n C) H. dThe genitourinary examination was remarkable for+ k5 `; s/ f4 S! _' l1 a& u. H
enlargement of the penis, with a stretched length of
G# ]' P: }( A/ b8 cm and a width of 2 cm. The glans penis was very well/ r, ^4 Q+ v- ]+ f: m/ G
developed. The pubic hair was Tanner II, mostly around
X i; x9 _7 C540
+ o: U! W2 ?3 ^% p4 o$ _$ ?5 gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from, k" E3 P6 y% I: D
the base of the phallus and was dark and curled. The
$ _- |2 Q2 @* ^3 ~$ n8 o+ ?# q8 ktesticular volume was prepubertal at 2 mL each.
g; y, e# r! c3 \The skin was moist and smooth and somewhat7 v. ]+ {) O( o! P
oily. No axillary hair was noted. There were no
$ g, t0 t) Q; Fabnormal skin pigmentations or café-au-lait spots.7 x0 J( l& L. j1 J- ?, z8 c! m
Neurologic evaluation showed deep tendon reflex 2+8 r2 C1 J- D/ \+ ?0 A
bilateral and symmetrical. There was no suggestion
' O: ~! i& ~' ~4 E* wof papilledema.3 |% c5 ~% L; ?! n
Laboratory Evaluation
K7 \) ^3 ]$ [. M) |The bone age was consistent with 28 months by5 M! ?' m: S9 [/ K8 ]
using the standard of Greulich and Pyle at a chrono-$ Q! k+ `# M' ^# N( f/ U* G
logic age of 16 months (advanced).5 Chromosomal
2 c I/ y9 A5 d1 @: ?0 |karyotype was 46XY. The thyroid function test
c2 i- s: K# s! |6 x+ K1 Zshowed a free T4 of 1.69 ng/dL, and thyroid stimu-. A( \% r, F! x4 M" ~0 D* U
lating hormone level was 1.3 µIU/mL (both normal).
, ?& q" T9 ?, n# b3 h3 n* ]2 Z& ~The concentrations of serum electrolytes, blood; ~) C& P' t$ l1 i* ]/ M9 n; Z
urea nitrogen, creatinine, and calcium all were
" R1 n# Y0 V$ |" Bwithin normal range for his age. The concentration* \4 V# P2 C2 t2 n% \( Q# h$ B L2 y
of serum 17-hydroxyprogesterone was 16 ng/dL
% ]) K9 W5 E( `/ k, F(normal, 3 to 90 ng/dL), androstenedione was 20" N5 ]; z* G" Y' q
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
6 l0 B. }: d0 q$ J! pterone was 38 ng/dL (normal, 50 to 760 ng/dL),5 b( c' K- U/ T& V& y3 q! r1 |1 F
desoxycorticosterone was 4.3 ng/dL (normal, 7 to# E* S, t, {9 b/ m: M3 t* Y- F0 b: E+ E. [
49ng/dL), 11-desoxycortisol (specific compound S)
# _. [( w2 b" Y z) nwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-) J3 r# _# M! v9 j% M! M+ ?
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
* T4 N# [- j( E9 Htestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
" W8 _" ^( T1 R1 a! Nand β-human chorionic gonadotropin was less than# v7 e8 m, E& [, {' [
5 mIU/mL (normal <5 mIU/mL). Serum follicular
; K* L/ S- P7 e+ l0 pstimulating hormone and leuteinizing hormone3 T$ g# C* g3 Q' S2 g- q! B4 U& b
concentrations were less than 0.05 mIU/mL
# P3 X1 R; \# k; m$ W(prepubertal).% ~, T9 N& Q& v% m$ |. z
The parents were notified about the laboratory
4 v6 L4 k5 l" V0 x5 K7 e: }* [results and were informed that all of the tests were5 L- A/ v* ^( T% u7 o4 \9 F/ f2 P( s
normal except the testosterone level was high. The
! U W: J% I* L1 x; q d, Xfollow-up visit was arranged within a few weeks to
4 T, `0 G& x0 I) ]% gobtain testicular and abdominal sonograms; how-' r! V9 a+ h8 V: j; d
ever, the family did not return for 4 months.7 o* a+ z. t' P5 ^! @
Physical examination at this time revealed that the
5 b- |2 h( ]9 f7 S" [6 R# Pchild had grown 2.5 cm in 4 months and had gained6 s1 p% J* |$ M1 Y
2 kg of weight. Physical examination remained
4 n `$ v; S3 Z V cunchanged. Surprisingly, the pubic hair almost com-
6 q1 n% e' n$ M) b! t4 ]pletely disappeared except for a few vellous hairs at
4 J O8 g! f4 c1 S% O9 ?the base of the phallus. Testicular volume was still 2* c! r% R8 |" ]' @2 R8 T
mL, and the size of the penis remained unchanged.
% d0 N' p1 B4 Z5 |6 M aThe mother also said that the boy was no longer hav-$ M, r" J, I/ z% L
ing frequent erections.
3 p) B6 \- G3 l3 u, C, k1 R- _Both parents were again questioned about use of
( r/ y) E* m! u2 V n+ Eany ointment/creams that they may have applied to. P/ r5 o2 j u4 B5 z2 K
the child’s skin. This time the father admitted the. a+ n/ v% T6 U. q5 A
Topical Testosterone Exposure / Bhowmick et al 541
9 {: ]+ v1 m3 R. M$ l3 U1 quse of testosterone gel twice daily that he was apply-
, N* [& T3 J$ }ing over his own shoulders, chest, and back area for) _1 f I" R/ z8 t* a, y& Y
a year. The father also revealed he was embarrassed
9 m6 X N" Y7 _, U Y8 T0 R9 Z# R/ t! yto disclose that he was using a testosterone gel pre-
' s( `, M% O" l6 s8 Qscribed by his family physician for decreased libido
; h) [) u# [9 e- w6 l7 ~secondary to depression.% U! J% |2 Y) v1 Y/ I
The child slept in the same bed with parents.
3 y% T, W* \3 H/ H CThe father would hug the baby and hold him on his1 t$ b0 k- ?* K
chest for a considerable period of time, causing sig-
/ J0 Q5 @! m0 L3 }7 enificant bare skin contact between baby and father.' W8 V% K6 [2 d4 }* n* Q, M& {1 h
The father also admitted that after the phone call,
3 v, M% W( F5 g$ i* dwhen he learned the testosterone level in the baby
9 k6 w& ?0 K4 Ywas high, he then read the product information
* M7 p% v- |& n2 M2 M! Rpacket and concluded that it was most likely the rea-- O0 |& h5 l2 o3 a" h
son for the child’s virilization. At that time, they
; b2 p; W! b. Ndecided to put the baby in a separate bed, and the
! {8 O( f9 M# Z8 c, qfather was not hugging him with bare skin and had. R5 g/ F( c0 P0 g' j l. z8 t! Y
been using protective clothing. A repeat testosterone
. { \2 d5 m: ^1 G$ M: Vtest was ordered, but the family did not go to the
1 s* F# y: w9 j! I- u, F/ vlaboratory to obtain the test.% L* |+ ^* s3 D- f9 l' t4 h
Discussion6 H. R# U4 ~/ c7 t
Precocious puberty in boys is defined as secondary' H U) ^" f' U" \6 |0 ~$ V$ R. T
sexual development before 9 years of age.1,4
$ ~6 v3 T" z: A0 X2 A, oPrecocious puberty is termed as central (true) when
4 ?- W( u- X6 pit is caused by the premature activation of hypo-
) B) \) o0 D; h: nthalamic pituitary gonadal axis. CPP is more com-4 y u) d- V9 W4 n
mon in girls than in boys.1,3 Most boys with CPP; P; H- @/ J: p
may have a central nervous system lesion that is
( I/ s; x, D: b5 }) o" cresponsible for the early activation of the hypothal-/ I& V# ]6 O2 X9 G, ^
amic pituitary gonadal axis.1-3 Thus, greater empha-
o+ Q( b0 o- U# B- f* ?sis has been given to neuroradiologic imaging in3 ?0 h& h o. L. c& |" O! V
boys with precocious puberty. In addition to viril-' A' ?+ E# m. `
ization, the clinical hallmark of CPP is the symmet-
S: s/ Z5 J9 t7 |6 T/ l: P9 Frical testicular growth secondary to stimulation by
$ N7 O U. b$ Egonadotropins.1,34 p, b) ]8 p1 P+ V9 O+ r; l l1 J
Gonadotropin-independent peripheral preco-) S* J7 D; c1 J. S
cious puberty in boys also results from inappropriate
8 k: @' H3 I/ r/ V& U4 randrogenic stimulation from either endogenous or
8 [0 r4 U! q. d# O% rexogenous sources, nonpituitary gonadotropin stim-
' W4 o0 K5 A4 F# D2 I- f Mulation, and rare activating mutations.3 Virilizing
* u7 e8 U6 `2 Ocongenital adrenal hyperplasia producing excessive
* a1 O" }9 b% B$ o* } radrenal androgens is a common cause of precocious
! n7 e" a0 v/ @: z# \" w8 fpuberty in boys.3,41 [+ U5 ~6 |0 M5 m* Q1 Y
The most common form of congenital adrenal
; E- ?, U y- e9 z2 khyperplasia is the 21-hydroxylase enzyme deficiency.
( B& ]6 {2 L# l/ }The 11-β hydroxylase deficiency may also result in0 H' v# M/ E0 {# y% Z5 ?9 C0 n0 L
excessive adrenal androgen production, and rarely,% W) b3 [+ g9 J" U& l* J6 M& A
an adrenal tumor may also cause adrenal androgen( n- w2 r% _! r( S# ?: |1 t
excess.1,3
8 v( K% b' X" M* A# w. B% k& z }at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from: R4 `# Z, q" A& q& h
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
9 v7 |) w6 h! f2 v' @- V! HA unique entity of male-limited gonadotropin-
- J/ I! D! d l, m" Z$ g7 gindependent precocious puberty, which is also known
- i; S) S5 w, ~/ f2 }# H, y$ F1 C% zas testotoxicosis, may cause precocious puberty at a$ A# p8 F# H8 V) @: q. n
very young age. The physical findings in these boys
% e+ U; ?% x9 C y" |with this disorder are full pubertal development,
" p) A" i2 h0 Jincluding bilateral testicular growth, similar to boys# T- z' v( N- f% E, c, `& g6 n
with CPP. The gonadotropin levels in this disorder8 g: r7 i; F8 K/ y, [2 ]) }; `, I; X
are suppressed to prepubertal levels and do not show
+ V v( {8 ]) Opubertal response of gonadotropin after gonadotropin-
* O0 ^7 s2 @$ ^/ |releasing hormone stimulation. This is a sex-linked5 o4 F* z3 |3 u1 h+ h" x# H9 u8 V
autosomal dominant disorder that affects only: s# M9 \1 q# p' V9 n
males; therefore, other male members of the family
4 v3 C9 ~- `3 i2 s5 Q0 Dmay have similar precocious puberty.3
( R, J1 A0 W% A3 hIn our patient, physical examination was incon-( W4 p/ O/ C2 g( h
sistent with true precocious puberty since his testi-
: w6 U* P& i3 L) ncles were prepubertal in size. However, testotoxicosis3 ~ x* R, g1 P! \ [3 v4 p
was in the differential diagnosis because his father- O! X9 Q* r& i/ T
started puberty somewhat early, and occasionally,# C/ \/ I& t" N. i$ j
testicular enlargement is not that evident in the0 Q& B: Z3 }! }9 u, X9 H/ @
beginning of this process.1 In the absence of a neg-
& t8 Q( B2 ]4 l. t/ ]; V3 eative initial history of androgen exposure, our
" Y8 i( Y5 |+ u/ I) Kbiggest concern was virilizing adrenal hyperplasia,: l; u1 h2 K3 f) R" H0 w: t
either 21-hydroxylase deficiency or 11-β hydroxylase
( m9 g8 B3 I+ s' ]/ V6 ~* hdeficiency. Those diagnoses were excluded by find-! A! O+ B8 O1 E+ a6 W
ing the normal level of adrenal steroids.
! p" `. s( ?/ xThe diagnosis of exogenous androgens was strongly% [, Z* j9 q! i# Z
suspected in a follow-up visit after 4 months because# b# m! A, n- s6 E$ a2 o3 G7 N
the physical examination revealed the complete disap-% @4 c. a6 z8 N/ Y! w& I6 b
pearance of pubic hair, normal growth velocity, and7 r S7 _0 V4 {
decreased erections. The father admitted using a testos-
a. I4 X- D# ]* t* dterone gel, which he concealed at first visit. He was; e. x2 w6 M7 N2 ]2 O# h% `8 I
using it rather frequently, twice a day. The Physicians’
6 L" N$ x2 B3 a/ tDesk Reference, or package insert of this product, gel or* s$ d9 L9 K5 D6 ~- Y
cream, cautions about dermal testosterone transfer to1 Q9 J: n1 X* V( l9 U& g
unprotected females through direct skin exposure.
7 B) [3 y! n; r: J/ rSerum testosterone level was found to be 2 times the
# ]) V$ V5 ]4 q( l8 Wbaseline value in those females who were exposed to
/ O8 }' I5 ~: e5 ]5 Meven 15 minutes of direct skin contact with their male V; F: z6 s3 s, Y9 {/ I1 ]- Q
partners.6 However, when a shirt covered the applica-
/ `5 `- Q* n i- t6 t% I: wtion site, this testosterone transfer was prevented.# M0 s7 o' ~8 |" |( S; |7 i; d
Our patient’s testosterone level was 60 ng/mL,
9 s0 m% S) E/ Y; owhich was clearly high. Some studies suggest that
2 L8 n9 v4 f3 b1 b' y$ mdermal conversion of testosterone to dihydrotestos-" }8 p y7 A, R, b% _& g
terone, which is a more potent metabolite, is more
' k o' M7 [2 U1 e. Q7 s! ~# |! Yactive in young children exposed to testosterone
, P0 @1 P" M" G' n( J4 w. q rexogenously7; however, we did not measure a dihy-
5 L" s! g2 B$ z! v1 adrotestosterone level in our patient. In addition to
9 w n- i" j1 s5 j( Pvirilization, exposure to exogenous testosterone in0 g+ X/ u' }8 k$ j
children results in an increase in growth velocity and
4 x/ d6 w4 q$ a" Z9 Gadvanced bone age, as seen in our patient.
: p0 J( T) r) F) T' Y3 X6 QThe long-term effect of androgen exposure during9 p! s# ]- ]% p$ k' r( r" o
early childhood on pubertal development and final
5 P) j& a0 t" ]3 L; k+ |: C' \adult height are not fully known and always remain! s- O5 T# k) j- q( _* y7 T
a concern. Children treated with short-term testos-
/ A* n; Z7 |( C& I# I& Y* Lterone injection or topical androgen may exhibit some
- H H' l- T/ y$ T4 U( J: zacceleration of the skeletal maturation; however, after) Q3 ^& t& A# R" q
cessation of treatment, the rate of bone maturation
5 l- J# e c1 M% s; |7 Zdecelerates and gradually returns to normal.8,9! \. K- Z3 Q. G2 \! A, }4 c; F& ^
There are conflicting reports and controversy
! V0 C& f+ A1 n dover the effect of early androgen exposure on adult3 ]8 w: o3 A" R7 Q
penile length.10,11 Some reports suggest subnormal: @( R! [4 q- r( k* s
adult penile length, apparently because of downreg-
# p! H/ {' N$ l- n5 Pulation of androgen receptor number.10,12 However,
7 h7 {# w' x$ ~. e' B. uSutherland et al13 did not find a correlation between3 e, v- a; J" ^/ @1 P
childhood testosterone exposure and reduced adult
, E9 K# v- \2 A4 f. fpenile length in clinical studies.. ]2 S. i9 c H8 b4 n! [$ O
Nonetheless, we do not believe our patient is6 e# v' N4 r3 F q4 G
going to experience any of the untoward effects from
8 X* _. }+ M* E; [testosterone exposure as mentioned earlier because
# k/ X, r5 Y8 W* p& ithe exposure was not for a prolonged period of time.! L$ d* V6 V8 f4 p& S8 U4 e; u q
Although the bone age was advanced at the time of. t5 I `; ?, z2 W! E2 A
diagnosis, the child had a normal growth velocity at; ~2 `4 ^ o$ G) s# t- e
the follow-up visit. It is hoped that his final adult" p: y2 a7 E: ^' `2 ^2 a
height will not be affected./ n' H! ^2 S3 q, O' Z2 ~
Although rarely reported, the widespread avail-3 e+ G1 M$ \2 L! ?% S) ?
ability of androgen products in our society may
: r! E7 ]; ]: windeed cause more virilization in male or female* L& n6 y6 P6 D8 Y
children than one would realize. Exposure to andro-
6 d* T a& w' G% g$ r" k) Egen products must be considered and specific ques-
6 P0 u* p/ S6 e# B4 k+ ptioning about the use of a testosterone product or
1 K" I2 g' D/ i3 {: w) V. [2 j: bgel should be asked of the family members during6 O7 Z0 n; ]% q: S- N% y3 M3 y
the evaluation of any children who present with vir-1 j S+ M, M3 P* A- g
ilization or peripheral precocious puberty. The diag-
! I& F8 s( r4 W5 ^, j5 lnosis can be established by just a few tests and by
" R. M- _9 ]7 `1 G* |" L( Aappropriate history. The inability to obtain such a
; F1 y7 E2 y( o+ p) l5 l7 chistory, or failure to ask the specific questions, may9 ]# L8 B4 o8 `
result in extensive, unnecessary, and expensive. o6 F1 L v, I4 ~! p& T0 V8 ]! F
investigation. The primary care physician should be$ \% u* }" S) u6 i
aware of this fact, because most of these children
, a2 P: q6 l- Z6 Jmay initially present in their practice. The Physicians’/ b3 J2 f4 X, j3 O j; k
Desk Reference and package insert should also put a/ Q! [/ |- P, n# x a0 B' N# ~$ [
warning about the virilizing effect on a male or
* C4 S+ X( p; g `' U* ~% ~female child who might come in contact with some-
) s( T0 }- c4 j0 E' }one using any of these products.) q2 J5 f$ U [2 W" h
References
* ?# F1 C- H! I, ^1. Styne DM. The testes: disorder of sexual differentiation
! M# g( v, V7 K) ]5 Y; e- t/ pand puberty in the male. In: Sperling MA, ed. Pediatric6 s8 v* l. U0 F( r+ S, m
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
) w3 L% {! X' A2002: 565-628.8 u. ?, X. l7 R1 C3 q& t$ |6 U
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious( J7 U6 D$ Q |8 O8 D R
puberty in children with tumours of the suprasellar pineal |
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