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Sexual Precocity in a 16-Month-Old
0 \- z- j" k1 @# wBoy Induced by Indirect Topical6 Z1 l2 s, d" A; b, P. x; s8 u
Exposure to Testosterone
. Z! z9 s4 u$ B. q. D1 G3 hSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2( X c' n8 u; ?% B _4 K+ t
and Kenneth R. Rettig, MD1
; c1 ]3 ] Z, O2 \! L0 H t" lClinical Pediatrics- K: D! e# G/ J+ R
Volume 46 Number 68 b" m5 H$ {& K' w
July 2007 540-543; F# W( f7 C' y9 P9 [( Y# a- F
© 2007 Sage Publications% _, y& b- m' K6 v+ h0 _9 P# A
10.1177/00099228062966510 r6 a6 b% z# x; x- j/ H9 Y8 C
http://clp.sagepub.com5 E, t; y- k0 F" |8 H
hosted at" z" a! |$ c* E
http://online.sagepub.com# l* B- w2 R& X' E2 d R/ j, v
Precocious puberty in boys, central or peripheral,0 I/ D/ U, Z i
is a significant concern for physicians. Central! L4 b [* b' _3 ~% l/ g8 h$ i
precocious puberty (CPP), which is mediated0 C }; {: |& u( G
through the hypothalamic pituitary gonadal axis, has
6 U3 |$ d& T( Ka higher incidence of organic central nervous system
9 ~$ ?( ]- Z+ l6 P) g& D$ Olesions in boys.1,2 Virilization in boys, as manifested
% b B3 j1 P7 Hby enlargement of the penis, development of pubic2 F W! d: J2 ~" f$ X$ L. c8 @; g# @
hair, and facial acne without enlargement of testi-2 R) \5 |2 |$ L# N; d, d9 D
cles, suggests peripheral or pseudopuberty.1-3 We
$ H) J/ m# N7 ~' @report a 16-month-old boy who presented with the
" [$ T$ p/ ^$ |6 k4 }3 denlargement of the phallus and pubic hair develop-- }# [7 V" ~2 h5 P3 K3 N5 w& Z
ment without testicular enlargement, which was due
; {1 b' K7 E% R6 b" A" Jto the unintentional exposure to androgen gel used by
/ N0 s6 j6 c3 p$ S+ Xthe father. The family initially concealed this infor-
) ]- F* A, @ Z% y, }2 Umation, resulting in an extensive work-up for this8 D: ~) i. P s/ L3 k! @$ g' a
child. Given the widespread and easy availability of t; w% a' L0 M& \$ U
testosterone gel and cream, we believe this is proba-
! x/ |' j, \ D. J9 _3 Q- cbly more common than the rare case report in the
w9 r7 k0 s1 \, D. eliterature.45 {; ]# u8 v5 v+ @# U9 D
Patient Report, G8 r& W- F* h# h# S5 n! b( F
A 16-month-old white child was referred to the
& n! C) w9 L) h( q* ^/ Mendocrine clinic by his pediatrician with the concern( B% V; V6 a' ]& P& I+ O/ w. M/ w
of early sexual development. His mother noticed
) n& W% m( M, Clight colored pubic hair development when he was0 k% w% X8 @3 `( o( P& }$ c
From the 1Division of Pediatric Endocrinology, 2University of& W8 P3 v& }$ m1 G6 w
South Alabama Medical Center, Mobile, Alabama.1 A( j" y- w) y. J
Address correspondence to: Samar K. Bhowmick, MD, FACE,
1 W, u/ z% b: l& qProfessor of Pediatrics, University of South Alabama, College of& H, G/ G9 [, `5 ~) C- o8 |" k8 z
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
) e2 H' C. o3 E2 s3 Q0 Ce-mail: [email protected].& }$ q% ^" T+ G& P' @6 ^1 A% Y
about 6 to 7 months old, which progressively became5 y% f- I! G7 l6 b# x. Z
darker. She was also concerned about the enlarge-
, @" J {* B$ O# W( |+ rment of his penis and frequent erections. The child
7 @$ V0 P8 e. qwas the product of a full-term normal delivery, with: O+ x# S; c1 K) @
a birth weight of 7 lb 14 oz, and birth length of! J) U! i: g( j1 q$ c) A5 N: L! o
20 inches. He was breast-fed throughout the first year- i* h: W3 E; {! c2 P
of life and was still receiving breast milk along with
/ C6 z2 v6 F7 a0 C" a. dsolid food. He had no hospitalizations or surgery,
! r% f9 F: N, H; R0 Kand his psychosocial and psychomotor development
8 k3 R' n* g9 l) D; Cwas age appropriate.
+ v: p" d+ w: O9 _; f, \The family history was remarkable for the father,- P/ ], c: l* ~
who was diagnosed with hypothyroidism at age 16,
: \) L2 Z5 g, }: \which was treated with thyroxine. The father’s
e2 h" U8 L; n; S. M; jheight was 6 feet, and he went through a somewhat- C. \. D. [3 j7 @. D/ a- M, Y
early puberty and had stopped growing by age 14.
8 \3 {$ p& a7 K' h- DThe father denied taking any other medication. The# e2 c3 U) a: H" S" ]
child’s mother was in good health. Her menarche4 i6 n: `+ G4 w/ A* K) b: V$ s1 p
was at 11 years of age, and her height was at 5 feet* y7 M+ d8 r9 D& w$ v
5 inches. There was no other family history of pre-
% d: E" ?8 K z8 A4 Pcocious sexual development in the first-degree rela-
: E6 Q! n/ a* A) q+ ?tives. There were no siblings.
% e5 ?1 q, s9 z& A2 y4 w- G* cPhysical Examination r2 Z( W' t8 d) V$ ?
The physical examination revealed a very active,
9 ?+ [* V" T# Y6 V4 Jplayful, and healthy boy. The vital signs documented" U" J1 W7 V. s% Q
a blood pressure of 85/50 mm Hg, his length was
% O: X/ M H L2 Y* V+ {' }& {90 cm (>97th percentile), and his weight was 14.4 kg6 S" o9 N9 W3 X
(also >97th percentile). The observed yearly growth* V6 ]! A/ |1 G: q- b1 M' B
velocity was 30 cm (12 inches). The examination of
( D) O/ h: p3 [the neck revealed no thyroid enlargement.9 d: z" X' Q6 M" Q, {2 y& t4 L
The genitourinary examination was remarkable for
2 D0 |# q0 q* F* Y, `2 Cenlargement of the penis, with a stretched length of' s$ ~2 _' K) W6 B' @
8 cm and a width of 2 cm. The glans penis was very well
, A' O6 u' C- R9 k3 y7 E# qdeveloped. The pubic hair was Tanner II, mostly around
, a! m4 |# c" O540
- E( h. l' k Bat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from* j' n; Q' j5 F/ \( t7 e* g* @
the base of the phallus and was dark and curled. The
8 c, T( {) H, r1 v M* s6 R) htesticular volume was prepubertal at 2 mL each.
( A" |7 Q- u7 T& e' eThe skin was moist and smooth and somewhat8 H3 W% S7 P: ?# X( x/ W% \4 D
oily. No axillary hair was noted. There were no
1 t# L i9 e' X$ | z# V% u. yabnormal skin pigmentations or café-au-lait spots.5 J f) V! Y7 N9 T
Neurologic evaluation showed deep tendon reflex 2+
" B, p( L4 D- q! C; Y- [: m2 \% U. F7 \bilateral and symmetrical. There was no suggestion! H4 s& _1 V# M3 o; [+ p% K$ U
of papilledema.4 z& v2 M9 {; [7 W, V. s
Laboratory Evaluation
; B/ Q4 ~/ ]* {6 r* oThe bone age was consistent with 28 months by
( D( n' }3 x3 z8 e N2 b. [6 o2 Y$ C) Busing the standard of Greulich and Pyle at a chrono-, M' k$ I5 W3 T) m
logic age of 16 months (advanced).5 Chromosomal
! }* j! i1 r# D) c, @; i# l8 Vkaryotype was 46XY. The thyroid function test
1 @1 {; T. j% P3 i) m$ B2 lshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
7 N4 b; U1 g/ ^3 v8 Wlating hormone level was 1.3 µIU/mL (both normal).3 \2 k/ h+ F; K5 P
The concentrations of serum electrolytes, blood5 C9 W+ p$ @' G8 R1 j
urea nitrogen, creatinine, and calcium all were
, M5 _$ |" G: M. D6 e' b! o% {8 hwithin normal range for his age. The concentration* M9 Q3 \7 } S
of serum 17-hydroxyprogesterone was 16 ng/dL
c- N) ?7 K; n+ X( A& L(normal, 3 to 90 ng/dL), androstenedione was 209 w* c! T6 T% h
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
" `$ W5 Z& u$ c4 Vterone was 38 ng/dL (normal, 50 to 760 ng/dL),9 N2 E- I/ @" ^3 q7 }/ }8 N
desoxycorticosterone was 4.3 ng/dL (normal, 7 to( i- `! o6 b( n3 i, I' j
49ng/dL), 11-desoxycortisol (specific compound S)
3 ^7 A8 i- X6 l2 _3 Y& Bwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-2 B% ^/ ? |/ E
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total, P/ m) k' b1 x/ @$ x3 ^
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),5 [/ u, p/ H" ~* k
and β-human chorionic gonadotropin was less than$ j4 Z' _! t! |! Y
5 mIU/mL (normal <5 mIU/mL). Serum follicular* F/ V( @; Q9 }& I4 m8 T1 e, D/ N: v/ Q
stimulating hormone and leuteinizing hormone- x: v+ [8 r2 s
concentrations were less than 0.05 mIU/mL
8 r7 T, D$ f- k(prepubertal).
& f3 w) L1 n9 n. {3 G1 hThe parents were notified about the laboratory L; C9 [# \/ _/ w4 \& E0 x
results and were informed that all of the tests were
: u; a4 j" [& M h, gnormal except the testosterone level was high. The
" ^, B( o: i( u- \5 X% p( R- lfollow-up visit was arranged within a few weeks to
2 l, P& c$ f" O. r9 \obtain testicular and abdominal sonograms; how-
5 Y5 M0 P% j: vever, the family did not return for 4 months.
3 I9 f; |) ~+ z% MPhysical examination at this time revealed that the4 h! U" k' G8 x
child had grown 2.5 cm in 4 months and had gained
7 V8 a0 I6 [' ^2 B q- L2 kg of weight. Physical examination remained
; V; Y3 I+ h: o/ r6 K* _unchanged. Surprisingly, the pubic hair almost com-, H/ S8 `* A: ?0 B: V
pletely disappeared except for a few vellous hairs at
1 W' W2 ~2 d1 B8 N1 o; G0 H7 E* H( Zthe base of the phallus. Testicular volume was still 2
7 r5 j& N8 ], T. x! b# W8 P2 b5 MmL, and the size of the penis remained unchanged.8 r! c! s( a: x" R* |+ p5 U
The mother also said that the boy was no longer hav-$ z6 ^. ^4 x2 R" k* J7 a7 c8 I
ing frequent erections.. s9 R4 W3 t0 v& k/ r: s! o& M; K
Both parents were again questioned about use of
t) v8 _! Z4 d3 x. Tany ointment/creams that they may have applied to: {* ]/ u. Z' J3 C/ R: L k4 m
the child’s skin. This time the father admitted the
9 |; A) A1 e2 J3 ~9 ZTopical Testosterone Exposure / Bhowmick et al 541' s% R) P! \9 ~
use of testosterone gel twice daily that he was apply-
1 _1 X' s" B5 x" J7 r+ ]- R# Cing over his own shoulders, chest, and back area for
9 I" F6 f% r/ M, u% s* ma year. The father also revealed he was embarrassed
& d% V0 z6 b X3 E( Lto disclose that he was using a testosterone gel pre-- Y) f- l3 r5 W, e$ z0 ^0 b
scribed by his family physician for decreased libido
: Y1 p W9 l7 [% k' Msecondary to depression.
& I1 I: C8 y# x. SThe child slept in the same bed with parents.
- f0 i8 C/ c7 j+ lThe father would hug the baby and hold him on his0 C# g8 K- |# i9 }& V, a$ u+ H1 y3 _
chest for a considerable period of time, causing sig-. X4 i' C3 U! i6 y2 k( m: s* T/ N
nificant bare skin contact between baby and father.
/ B7 \& `! b% NThe father also admitted that after the phone call,: o; i1 \0 Z9 c8 q) o* @4 F1 I7 @
when he learned the testosterone level in the baby F) h" }8 J8 @1 Y9 F
was high, he then read the product information, N; j# a* f I6 L3 a& u) U
packet and concluded that it was most likely the rea-* E' H2 d; E2 ?: ^
son for the child’s virilization. At that time, they
; ~) v+ \" m5 ?4 o3 N" @+ ndecided to put the baby in a separate bed, and the0 T* i5 \) l6 r! t& E
father was not hugging him with bare skin and had
, a- T/ Z+ z+ @4 A, D) Qbeen using protective clothing. A repeat testosterone- Q4 z+ Q5 W ?1 C" c5 }
test was ordered, but the family did not go to the" t- m7 `8 B; y' i- L
laboratory to obtain the test.
6 Z# J, H ^( G! B% D- DDiscussion0 ]" a! E: ]! j/ G; g7 {6 r4 I& e/ i
Precocious puberty in boys is defined as secondary. |% U. v% g2 c& Z2 J8 N: d
sexual development before 9 years of age.1,48 C' ]% c2 _* V) d X$ k" U
Precocious puberty is termed as central (true) when& U" @6 [+ F; g5 ~+ U4 i
it is caused by the premature activation of hypo-
) a" m* Q2 S+ {' T) ^1 w* ?( W5 }thalamic pituitary gonadal axis. CPP is more com-& u! N" F" ?% q7 m" X4 X
mon in girls than in boys.1,3 Most boys with CPP" W: M2 @- f4 N
may have a central nervous system lesion that is
1 K6 G6 b8 M3 e9 e# d8 |4 H0 `2 Nresponsible for the early activation of the hypothal-
" ?; H c1 c3 Camic pituitary gonadal axis.1-3 Thus, greater empha-
; F- L+ W$ v7 |0 R1 ^sis has been given to neuroradiologic imaging in" R' H3 q/ p+ i' I
boys with precocious puberty. In addition to viril-. B4 W* W1 K% K1 ]+ M
ization, the clinical hallmark of CPP is the symmet-
7 o8 j2 O& x( }- s i. l* Qrical testicular growth secondary to stimulation by
/ b- R6 v# H3 Agonadotropins.1,3
7 C6 v+ H1 x0 jGonadotropin-independent peripheral preco-
) [: a% A2 P5 R6 `+ zcious puberty in boys also results from inappropriate; Q6 ^/ J( z2 D6 P! N+ n1 u
androgenic stimulation from either endogenous or
# s; j. ]. _$ I% i: R0 ]; O1 U! n5 texogenous sources, nonpituitary gonadotropin stim-4 M* @( d/ ]+ N' _" b) f2 C+ I0 k8 s! F
ulation, and rare activating mutations.3 Virilizing
6 G! `3 Z) d+ E/ ]8 ocongenital adrenal hyperplasia producing excessive
( K: M T* ^& u) o* V# m6 Dadrenal androgens is a common cause of precocious& a! _( o" }$ ]
puberty in boys.3,4, Z9 J S, g4 O* j/ N3 T3 D# n$ G9 i2 H
The most common form of congenital adrenal' H* v2 l' i. ?8 W' J; K
hyperplasia is the 21-hydroxylase enzyme deficiency.9 h: K. f7 o# p7 ^$ R3 o
The 11-β hydroxylase deficiency may also result in7 g% o+ R7 ^/ }4 s( J3 n
excessive adrenal androgen production, and rarely,* n* |: h' L3 v% x. ~
an adrenal tumor may also cause adrenal androgen
. m9 J0 M9 f+ M- Rexcess.1,3/ v% q9 Z( C/ {+ I6 @
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from0 x0 Z0 k2 G4 U* Q
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
" ?0 ~- E- ?# G8 u4 c) GA unique entity of male-limited gonadotropin-
6 G* I4 b% I9 F7 _: A! o5 Lindependent precocious puberty, which is also known
1 [) N4 T) P( o4 K' Ras testotoxicosis, may cause precocious puberty at a
6 Y2 i# l. m# cvery young age. The physical findings in these boys3 v" E) S% J0 V
with this disorder are full pubertal development,5 Z4 { e2 \6 _1 g
including bilateral testicular growth, similar to boys
* i- _) H* Q& O4 e8 }: S) K. iwith CPP. The gonadotropin levels in this disorder
, l! h' \6 Q0 K. kare suppressed to prepubertal levels and do not show
) p( U& `# U5 Y7 M( i r" l$ o% Z2 ipubertal response of gonadotropin after gonadotropin-
6 G- c4 ^2 |9 Hreleasing hormone stimulation. This is a sex-linked/ |. v3 D: T2 M5 d* o) R
autosomal dominant disorder that affects only
; r, s. g6 _7 X' b$ ^5 q; `males; therefore, other male members of the family
E5 K) [( ], qmay have similar precocious puberty.3
* L2 Q- g1 c( E" I" nIn our patient, physical examination was incon-6 W/ V. C" j( F
sistent with true precocious puberty since his testi-
- g! o0 ]0 | j r" Icles were prepubertal in size. However, testotoxicosis
1 M6 y8 c1 T" R4 \2 C2 H, P/ vwas in the differential diagnosis because his father
' s% |8 [( |) Y$ B( Zstarted puberty somewhat early, and occasionally,; t0 Z9 M' [: b5 I
testicular enlargement is not that evident in the
; T8 h+ T5 I& c7 ~9 ?beginning of this process.1 In the absence of a neg-
& Y6 ~ s% P) Y% F! v3 zative initial history of androgen exposure, our
* T: M! I' t& jbiggest concern was virilizing adrenal hyperplasia,, Z5 a5 o7 A J- t$ S
either 21-hydroxylase deficiency or 11-β hydroxylase6 u3 s1 A3 T4 Z9 ]" [, I+ R
deficiency. Those diagnoses were excluded by find-
. K5 Z4 t# e7 e2 V* S. wing the normal level of adrenal steroids.$ C r' s6 J" J; B8 a4 G/ i" b' J2 ~
The diagnosis of exogenous androgens was strongly( D0 C" \+ ^, G" x9 Q
suspected in a follow-up visit after 4 months because
- Q9 v: m j, vthe physical examination revealed the complete disap-5 `' A' g; H1 m
pearance of pubic hair, normal growth velocity, and
4 {! x5 y0 i, S; d/ U6 }) }' y/ Mdecreased erections. The father admitted using a testos-6 B3 H% C6 s7 K( o- ^, o x
terone gel, which he concealed at first visit. He was
. ~) B8 Y. L# eusing it rather frequently, twice a day. The Physicians’3 P& L8 y( p$ _7 D# m
Desk Reference, or package insert of this product, gel or
9 s* u; T0 u4 O8 X) Q& @* \cream, cautions about dermal testosterone transfer to( @ q7 ^' b- A
unprotected females through direct skin exposure.
. @2 o$ m7 F$ i9 K. S9 |Serum testosterone level was found to be 2 times the# v- [$ k# X9 w' z/ g8 f% E9 e) H4 b
baseline value in those females who were exposed to( k2 |) R! s9 A7 G# V: j4 U0 @
even 15 minutes of direct skin contact with their male5 ?+ E; N- d7 L. I
partners.6 However, when a shirt covered the applica-2 |3 {( Q+ q+ z$ m& [: h$ Y
tion site, this testosterone transfer was prevented.
( b6 L+ D5 |2 V3 |4 s. ]4 gOur patient’s testosterone level was 60 ng/mL,6 F' h1 \/ o2 b
which was clearly high. Some studies suggest that" F3 M& ]) h+ K
dermal conversion of testosterone to dihydrotestos-* y) F+ r/ \6 f- z
terone, which is a more potent metabolite, is more
` s$ f; k, u9 _& h% oactive in young children exposed to testosterone; D" V, H B0 O* b
exogenously7; however, we did not measure a dihy-
; k4 i: o3 F% K! p" A V$ rdrotestosterone level in our patient. In addition to: X( H2 y) b$ J+ Q
virilization, exposure to exogenous testosterone in
, y# P0 s9 u+ B; u% vchildren results in an increase in growth velocity and2 Y" T! j8 R0 G
advanced bone age, as seen in our patient./ Z- y. c. g" k
The long-term effect of androgen exposure during
/ P ?3 w, J: [0 o3 cearly childhood on pubertal development and final* }+ F9 R3 B: q2 g3 } a, k
adult height are not fully known and always remain
/ {- ^$ _: y- s0 g% e$ u5 N; Ta concern. Children treated with short-term testos-
6 W, Q3 Q4 r! vterone injection or topical androgen may exhibit some1 E# n2 o' ]: t3 {0 j
acceleration of the skeletal maturation; however, after
" t5 r0 l1 B8 b. Jcessation of treatment, the rate of bone maturation+ e; T+ Z. f* o. g+ q
decelerates and gradually returns to normal.8,9
/ E9 z6 T+ P" M' z: g$ TThere are conflicting reports and controversy
* W- Q$ a3 x% D5 [) ]: u! Pover the effect of early androgen exposure on adult. m2 Z$ \! ?# S1 j) E% j" w5 t
penile length.10,11 Some reports suggest subnormal
2 `' y, S& U! H' q0 `2 zadult penile length, apparently because of downreg-. k6 \, S& r! t1 ^! U
ulation of androgen receptor number.10,12 However,
% C6 t- n8 P ]/ BSutherland et al13 did not find a correlation between* J X- g+ Q( K& s
childhood testosterone exposure and reduced adult, `' m( ^+ Z3 }* b3 R1 h
penile length in clinical studies.- C8 b7 y0 k$ T+ F8 w5 ?1 J9 I# C( G
Nonetheless, we do not believe our patient is* j' a' R2 e: u6 s9 u3 {2 R: ]
going to experience any of the untoward effects from- M3 I* i! Y% w% s( r1 }8 W
testosterone exposure as mentioned earlier because
, `: V6 t* N; \the exposure was not for a prolonged period of time.
! X6 q$ n* z# k6 vAlthough the bone age was advanced at the time of/ }6 i4 n0 I2 g1 H0 r0 c
diagnosis, the child had a normal growth velocity at
5 i% d. o/ b7 A% nthe follow-up visit. It is hoped that his final adult" p6 r. I5 s3 F* Z
height will not be affected.
s) r6 o- N, `: HAlthough rarely reported, the widespread avail-' u% i3 N/ Z4 K0 c" o' o9 ~
ability of androgen products in our society may
4 F, O' L+ j) x) ] Windeed cause more virilization in male or female
% X8 p9 K8 p1 A3 q2 v4 t' x9 f9 pchildren than one would realize. Exposure to andro-
. y0 B2 S! A9 |( S, `+ A0 X3 J/ \gen products must be considered and specific ques-( y; `, ]9 K' d" [$ {0 S/ e
tioning about the use of a testosterone product or
+ _1 L2 f; f+ i7 }. p1 G) \& x; mgel should be asked of the family members during
& b, p4 e+ B# B+ jthe evaluation of any children who present with vir-3 s; R# B: _' Z K2 `7 O; {5 I/ c
ilization or peripheral precocious puberty. The diag-
( ?% p) X/ Q: ?3 D. Vnosis can be established by just a few tests and by
' Z" z4 P, Z3 e9 Y) r9 s& P9 ~% Rappropriate history. The inability to obtain such a
$ Y6 c( _+ R! G$ D- C5 }" Q3 Fhistory, or failure to ask the specific questions, may8 ^/ W. ^9 ~" j2 h
result in extensive, unnecessary, and expensive
9 ^+ ^& t5 { Dinvestigation. The primary care physician should be
: U' U; c( J$ ^# P U+ eaware of this fact, because most of these children
2 F& U* t0 ]6 H d3 L3 j' T' jmay initially present in their practice. The Physicians’
! E2 @- u. x- q0 TDesk Reference and package insert should also put a
% s* J/ \; X. L0 B1 X) dwarning about the virilizing effect on a male or: T- G) Y! Z) D; g( g1 o! k
female child who might come in contact with some-( q, G8 @1 D( y- G/ Y% f
one using any of these products.0 C9 B. ]2 @: L6 o
References1 U" h1 ~* q- D( V7 i
1. Styne DM. The testes: disorder of sexual differentiation. }3 `6 u% `0 d( F+ A6 Z
and puberty in the male. In: Sperling MA, ed. Pediatric# v* Q5 k3 R' n/ G9 H, Z
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
* t( Z: @7 ]) j0 z2002: 565-628.
/ z6 o4 ?, q x9 A u2 X- Y ?2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
. W" ?- d( Z. v/ w# ^! Xpuberty in children with tumours of the suprasellar pineal |
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