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Sexual Precocity in a 16-Month-Old
& y v6 Z# \6 w0 G8 G! IBoy Induced by Indirect Topical+ Z+ C* l! ]- n8 [' X( d- ]
Exposure to Testosterone# n) h9 G8 z0 R" ^+ U7 k7 V
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
0 D& R0 w) ? j1 i8 a- q% Uand Kenneth R. Rettig, MD1/ E- X- j/ `5 @$ j/ O$ i
Clinical Pediatrics
; N! C% i/ } Q: N& e3 W, iVolume 46 Number 6
8 ]0 \" z: C' ^% Q2 W% K% ~July 2007 540-5434 t8 d9 A' G# ]8 Z' b. ]
© 2007 Sage Publications
( F5 d4 ?, G9 l q2 |10.1177/0009922806296651/ x# N9 R1 l/ Z7 [4 D) t0 l$ k
http://clp.sagepub.com. P/ @! e# u1 z1 q$ t' M+ b5 p
hosted at
7 ] D3 Q! q7 P: j8 k; Q" shttp://online.sagepub.com- M6 {) x9 z* N- T- l
Precocious puberty in boys, central or peripheral,
; n8 x/ R" N8 y4 ?1 \, V2 ~( Lis a significant concern for physicians. Central9 { B( D( g, K) U+ [( s
precocious puberty (CPP), which is mediated
( R/ i, Q" G: f$ C6 {/ b5 dthrough the hypothalamic pituitary gonadal axis, has
; P" N) t$ t9 T/ }% C6 M3 Ca higher incidence of organic central nervous system
. |( ]" S e: K/ o, W$ Klesions in boys.1,2 Virilization in boys, as manifested X1 _8 J0 i9 o' U( A# A: ^
by enlargement of the penis, development of pubic
G- j4 A' v; `6 Ghair, and facial acne without enlargement of testi-# i# i8 ~0 g6 u t. T/ y
cles, suggests peripheral or pseudopuberty.1-3 We
- E2 h, B K% N% \: f, Lreport a 16-month-old boy who presented with the+ N/ h* i# S' j- h5 h/ l% u& C
enlargement of the phallus and pubic hair develop-3 g H9 L& u4 {% n. T! q. c: C
ment without testicular enlargement, which was due) ~5 c4 x. {8 _ e4 A
to the unintentional exposure to androgen gel used by6 s7 u8 c5 L, O) ~1 b* R' y+ G( }
the father. The family initially concealed this infor-
( F2 j& Z; B0 Pmation, resulting in an extensive work-up for this
% Q6 ~0 e7 N# n- ]% mchild. Given the widespread and easy availability of
& r0 h6 \: F% E. Vtestosterone gel and cream, we believe this is proba-
( u% s) f( [, s" S8 I6 S& Qbly more common than the rare case report in the! ~9 V; O! E1 e( G* G
literature.42 g8 h1 Z( ?7 k
Patient Report% K* n h+ `# {. [
A 16-month-old white child was referred to the
) i9 |* ? ?/ ?! V) fendocrine clinic by his pediatrician with the concern d9 F, I$ R9 y* D: x g+ m9 d
of early sexual development. His mother noticed/ @! i4 {7 v0 ]9 L" u" W
light colored pubic hair development when he was
' f" S. H H( l" I0 F: YFrom the 1Division of Pediatric Endocrinology, 2University of3 r0 x0 M9 w+ U4 p& p* j" |. N: J
South Alabama Medical Center, Mobile, Alabama.
/ y$ o1 f8 @/ S& h5 \! vAddress correspondence to: Samar K. Bhowmick, MD, FACE,
1 U8 B* I f' b. [' {- _Professor of Pediatrics, University of South Alabama, College of
6 U% h9 M- j) k: CMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
. V, T4 G: N, b, R1 \e-mail: [email protected].
D- r+ @1 ]! A o3 U: \about 6 to 7 months old, which progressively became
* {3 t1 U" K1 P$ i' K2 Mdarker. She was also concerned about the enlarge-
) i' F0 C: f; jment of his penis and frequent erections. The child
$ R3 ~' k5 Q8 n6 m* X* F: ]was the product of a full-term normal delivery, with
( b. j0 t7 R1 Ka birth weight of 7 lb 14 oz, and birth length of
2 M8 U7 l+ q9 C; x20 inches. He was breast-fed throughout the first year9 I: u; ~4 y v7 R* s" z$ x
of life and was still receiving breast milk along with( [5 l: S! j# o L& ?/ q
solid food. He had no hospitalizations or surgery,
: G$ n" L W% S. K9 i. `and his psychosocial and psychomotor development
( q, E( }: O- E& M. Gwas age appropriate.4 w) i" `9 _0 m. F
The family history was remarkable for the father,
+ O; s" P4 l: G8 |who was diagnosed with hypothyroidism at age 16,) p9 ]7 z7 ]( P
which was treated with thyroxine. The father’s
7 j& P' i# E( \$ bheight was 6 feet, and he went through a somewhat- z9 x D) D7 C8 x# Z7 r
early puberty and had stopped growing by age 14.
4 g2 g+ E0 m$ n" xThe father denied taking any other medication. The( o. F. ^4 ^+ c" B, L5 H
child’s mother was in good health. Her menarche5 t- d9 }- H$ K2 @' P
was at 11 years of age, and her height was at 5 feet5 H, K0 g& I. ? h$ R9 F3 |/ P+ x n
5 inches. There was no other family history of pre-! P9 N% s# u O1 s
cocious sexual development in the first-degree rela-! e7 F7 W1 n/ n( Q) O% Z( s" ^4 X" `
tives. There were no siblings.) V7 Q6 l7 Q a5 ]1 W# j0 G
Physical Examination
y2 D; ^7 l! v* V4 j3 nThe physical examination revealed a very active,
) Q P! f0 m+ S+ d" qplayful, and healthy boy. The vital signs documented8 R6 R$ z3 O+ A% u* n s" Z
a blood pressure of 85/50 mm Hg, his length was
! p; D- F) q# O6 H$ q% s! m90 cm (>97th percentile), and his weight was 14.4 kg
" s9 ^! Z1 i' L% H0 Z+ Q(also >97th percentile). The observed yearly growth9 i; K4 o" D: P
velocity was 30 cm (12 inches). The examination of
" z+ A# t1 L0 w+ ^the neck revealed no thyroid enlargement.% J7 c! |/ [7 ]7 b/ E
The genitourinary examination was remarkable for
1 _# ~' t8 @1 ^( R# H; Penlargement of the penis, with a stretched length of
2 `. o5 e* B! }9 ^7 m2 T, k8 cm and a width of 2 cm. The glans penis was very well, ^, }/ ]5 P4 N4 }
developed. The pubic hair was Tanner II, mostly around
7 Z! ~8 @" g& u- ^540' }! f( x' E: x$ D
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
9 A! R0 i% e9 ithe base of the phallus and was dark and curled. The
7 U. m" z& u9 q5 E) |testicular volume was prepubertal at 2 mL each.
0 e2 r; d) L6 W/ Y) t. M% ~1 aThe skin was moist and smooth and somewhat
" l! B9 ~ R6 Q. r* ^( a, Zoily. No axillary hair was noted. There were no
/ j1 H3 N6 v; }4 @$ ]% h8 Pabnormal skin pigmentations or café-au-lait spots.+ L6 X3 U& b% L4 k' x2 b
Neurologic evaluation showed deep tendon reflex 2+) I$ e0 h- m/ }, k
bilateral and symmetrical. There was no suggestion" E: ?9 A) Q2 K6 n! p \) v
of papilledema.
+ r; x" V& b: W! q0 b( nLaboratory Evaluation
( a, E6 t2 p( |The bone age was consistent with 28 months by. k# ^/ v: Z) M3 C
using the standard of Greulich and Pyle at a chrono-4 O& G. r& }7 f* U# x
logic age of 16 months (advanced).5 Chromosomal( M" g- B+ H9 G2 S7 N5 x A0 S
karyotype was 46XY. The thyroid function test# V; z' V- h5 C& o
showed a free T4 of 1.69 ng/dL, and thyroid stimu-1 v$ u6 p4 b, q- V' ?2 c
lating hormone level was 1.3 µIU/mL (both normal).
* Z8 \7 Q0 H& \5 e( a9 g3 [+ S, Y. x0 GThe concentrations of serum electrolytes, blood
/ j+ |, S6 g% Z! `0 E! m, d) xurea nitrogen, creatinine, and calcium all were2 [5 I6 `0 q3 V2 d: x; j- M
within normal range for his age. The concentration
2 m/ e: Q0 { u5 `5 A( vof serum 17-hydroxyprogesterone was 16 ng/dL% C( w* c( t/ Q* D4 L# c0 g
(normal, 3 to 90 ng/dL), androstenedione was 20$ N( A6 ^9 r; H3 o* R
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
7 T% ~6 `- q" S3 t" Eterone was 38 ng/dL (normal, 50 to 760 ng/dL),6 d2 d/ M/ P E2 N
desoxycorticosterone was 4.3 ng/dL (normal, 7 to
: H5 i) M# N% K9 H49ng/dL), 11-desoxycortisol (specific compound S)
- h3 j! v7 Y2 U9 _& o+ F" Swas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor- S( _7 ]( `- M U7 s/ m
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total7 F) I- ?* f8 g
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),
; h) i. o `8 V) Y- Mand β-human chorionic gonadotropin was less than
8 C) Z: t3 V1 X5 mIU/mL (normal <5 mIU/mL). Serum follicular: Z4 e) d- A2 B3 w3 @6 o4 v
stimulating hormone and leuteinizing hormone
% C9 B! b* k8 B qconcentrations were less than 0.05 mIU/mL
; d5 `( \" {! q7 B( s% R+ K(prepubertal).* y4 z+ \( v! t$ v, d. Y
The parents were notified about the laboratory. W- K! [8 \% u7 T4 C! l
results and were informed that all of the tests were
8 `( m* a! k- ]$ Hnormal except the testosterone level was high. The7 i: d- [: y; Q' G( z
follow-up visit was arranged within a few weeks to
9 n; N4 H* ^6 i) r2 r; @7 B# t% A7 zobtain testicular and abdominal sonograms; how-
* J g2 D5 T9 E( Y( c6 a% G7 dever, the family did not return for 4 months.
+ C* v$ E e3 N% }Physical examination at this time revealed that the) t8 r3 h4 C& E4 C) v+ Y5 q
child had grown 2.5 cm in 4 months and had gained
, s9 @! f, ]1 X) W7 I0 J* g) z2 kg of weight. Physical examination remained
- w3 y4 H( N* junchanged. Surprisingly, the pubic hair almost com-
7 t$ I" b4 Y; D5 C( Bpletely disappeared except for a few vellous hairs at1 O( C, N% M" Q# @* F m
the base of the phallus. Testicular volume was still 2
: x+ O, G+ d/ M3 S! KmL, and the size of the penis remained unchanged." n, t1 H1 a( d y( D* E8 x" D; `
The mother also said that the boy was no longer hav-
9 c$ [ b/ P3 j2 sing frequent erections.- y3 I1 ~1 ~" v3 \
Both parents were again questioned about use of
+ z* r# R8 t- Z6 Tany ointment/creams that they may have applied to
6 z; t0 Y, P& I/ }5 dthe child’s skin. This time the father admitted the3 s: k5 w o( V$ k
Topical Testosterone Exposure / Bhowmick et al 541
; r4 u6 A9 B; ouse of testosterone gel twice daily that he was apply-
M, H) D, o8 K. Qing over his own shoulders, chest, and back area for
4 N8 m' P6 z) ]% H% g. O1 V4 za year. The father also revealed he was embarrassed
8 v: t$ ?; ?/ t' kto disclose that he was using a testosterone gel pre-7 w; }3 \' Y% l; s5 b: ?6 p' s2 u5 M
scribed by his family physician for decreased libido K2 t9 M! z; I/ U
secondary to depression.9 t7 B1 i, F- ]
The child slept in the same bed with parents.
- }4 L: l- S- ^The father would hug the baby and hold him on his$ L; L7 I+ I' I( m* j
chest for a considerable period of time, causing sig- {/ K* J5 z5 U3 P1 J/ V
nificant bare skin contact between baby and father.# @+ y8 R$ T9 w# d# f2 ?! l( w( @% i
The father also admitted that after the phone call,
9 C" s2 I0 |2 c4 q% xwhen he learned the testosterone level in the baby, h' m d8 P' v! g$ A
was high, he then read the product information
8 [( }! n4 X/ k$ O/ x9 P6 Ppacket and concluded that it was most likely the rea-
5 d( t2 C4 \+ S+ Z& dson for the child’s virilization. At that time, they9 z: c; E; [1 W: V3 F
decided to put the baby in a separate bed, and the: F8 z, U: J6 r2 C- k* T- {
father was not hugging him with bare skin and had
+ t, V. }# L: Mbeen using protective clothing. A repeat testosterone
, j% `, }1 |9 @; T! E' U4 `test was ordered, but the family did not go to the
* e$ K' D5 u6 Wlaboratory to obtain the test.
% r3 N* c% h! z0 `- a$ O% TDiscussion- J9 Y% P. t- H& |: t
Precocious puberty in boys is defined as secondary8 s! X9 r" k0 T3 z8 r( G" a
sexual development before 9 years of age.1,4
" `' z. S, z. E) o/ rPrecocious puberty is termed as central (true) when0 O: f7 N# F, i* q3 Q" q$ d8 d
it is caused by the premature activation of hypo-
/ c/ ?" [$ W# B* G% p9 nthalamic pituitary gonadal axis. CPP is more com-
7 t4 e9 ~) ]6 c9 T7 e& _; omon in girls than in boys.1,3 Most boys with CPP
. {, o# s4 q a# r9 l) p, S# Jmay have a central nervous system lesion that is
) B/ P& W# \2 s1 Q3 g2 I4 ?6 Jresponsible for the early activation of the hypothal-% v4 C; P& a2 d) i+ A: W2 A5 G4 u
amic pituitary gonadal axis.1-3 Thus, greater empha-
b8 \$ o$ L% s0 o. I7 Tsis has been given to neuroradiologic imaging in
2 `* @$ `: @% w" j: lboys with precocious puberty. In addition to viril-, j0 k$ Q( g" Q' j/ q8 g/ o0 Z/ {
ization, the clinical hallmark of CPP is the symmet-* X" D: t4 x; Q: B9 R5 Y" A# P
rical testicular growth secondary to stimulation by+ D% C! h! d* V, z! O
gonadotropins.1,38 M- X) P- {6 G9 i& g: z5 `; f
Gonadotropin-independent peripheral preco-
; W) t3 M/ R4 e R$ b. Jcious puberty in boys also results from inappropriate
7 R7 r2 L4 F/ X+ a, Uandrogenic stimulation from either endogenous or1 V- B2 ^( Y3 K6 a1 \1 H
exogenous sources, nonpituitary gonadotropin stim-
5 z- E9 B, N. n9 @ulation, and rare activating mutations.3 Virilizing t2 s' _" e/ r# s# i! i4 p
congenital adrenal hyperplasia producing excessive( l1 S* k3 z$ o0 Y& `4 E& v
adrenal androgens is a common cause of precocious* D/ @3 y. y3 k6 _8 T
puberty in boys.3,4
8 G H; X/ X' h- d: w+ m( {The most common form of congenital adrenal/ u% r" }5 M, s* X- m
hyperplasia is the 21-hydroxylase enzyme deficiency.
9 C/ ~1 l# z7 @. m/ r. E! Z6 j- ~The 11-β hydroxylase deficiency may also result in* M9 |7 }2 X4 @# R5 d" p
excessive adrenal androgen production, and rarely,0 M. x/ D9 _' x( [# z6 A
an adrenal tumor may also cause adrenal androgen
: E: W l1 Z" h. \, r! ]! yexcess.1,3: w0 t6 S8 G5 m7 m0 D8 ~
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from+ l& d' u# h t \
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
( P0 F/ |- r; ~- z C: aA unique entity of male-limited gonadotropin-' |" m" p0 U5 ?+ s
independent precocious puberty, which is also known8 ^$ i- S# Q6 D, b- O3 o# [
as testotoxicosis, may cause precocious puberty at a9 d2 w) `+ @- B% N
very young age. The physical findings in these boys
+ r: k1 B# P; D; cwith this disorder are full pubertal development,0 h. `% [ g" ?9 \) ~0 W: q1 T
including bilateral testicular growth, similar to boys
+ m0 B Q7 h5 g6 a0 ^$ J! P$ Q* `with CPP. The gonadotropin levels in this disorder
" E5 n e( j) b- m- d% Lare suppressed to prepubertal levels and do not show
4 B5 ?2 Y6 P& t( _5 b+ j: R1 ]pubertal response of gonadotropin after gonadotropin-
P0 T* `" X5 }$ A, x+ a0 }releasing hormone stimulation. This is a sex-linked/ b. H% j$ {9 [6 Q
autosomal dominant disorder that affects only
' a- K' \* F5 c: m8 o2 emales; therefore, other male members of the family* L7 t# ]3 M0 b9 D
may have similar precocious puberty.3' F2 E5 t* X! |- ]/ @" a! L* r' R
In our patient, physical examination was incon-! [) A$ }% S- f% i
sistent with true precocious puberty since his testi-
5 P/ K9 ]4 D9 ccles were prepubertal in size. However, testotoxicosis) p* g6 g+ N ?/ w' f0 I/ D! ~
was in the differential diagnosis because his father" j; y# l+ H$ F( ~* T. x, W2 N3 ~
started puberty somewhat early, and occasionally,
~/ g4 d+ m; o! A% \) M, d2 Itesticular enlargement is not that evident in the
# {' z' `5 i0 |! w) [8 Jbeginning of this process.1 In the absence of a neg-% |3 Z) {0 J; d$ f7 g8 k
ative initial history of androgen exposure, our
- P* ^& l( T1 S* abiggest concern was virilizing adrenal hyperplasia,
- I& E) b9 o5 \( S( leither 21-hydroxylase deficiency or 11-β hydroxylase s' Y& u" ]# G7 u
deficiency. Those diagnoses were excluded by find-1 l$ e8 o/ s6 F U
ing the normal level of adrenal steroids./ W7 q/ Z' l4 C0 {- E; t7 U; D
The diagnosis of exogenous androgens was strongly
) e: p* [7 {- R! o" e; tsuspected in a follow-up visit after 4 months because7 K* e2 @4 j7 ~/ p2 c' W* d
the physical examination revealed the complete disap-# [3 x( H& d* j' m& C* e
pearance of pubic hair, normal growth velocity, and
: V7 ?' @7 a5 U; q8 |2 H: x+ l; Mdecreased erections. The father admitted using a testos-4 s1 w) D9 C% X+ h% J) H
terone gel, which he concealed at first visit. He was
7 b1 U7 g9 h' v# B; D& Ausing it rather frequently, twice a day. The Physicians’
/ o8 [& k4 m* z# \Desk Reference, or package insert of this product, gel or9 k. N/ R; B9 E. _! ^! l
cream, cautions about dermal testosterone transfer to
& C6 H. j/ C4 L# Cunprotected females through direct skin exposure.: z. B8 v# x1 D% w# J. v
Serum testosterone level was found to be 2 times the4 i# ~3 i. S* P3 a
baseline value in those females who were exposed to8 l: h9 z. C+ Z- x9 ?
even 15 minutes of direct skin contact with their male' F5 \ C, O, H6 a- M7 K
partners.6 However, when a shirt covered the applica-: B; {3 N, [8 F* [7 x. \+ p
tion site, this testosterone transfer was prevented., W( A1 A: U% ~6 S5 y* a
Our patient’s testosterone level was 60 ng/mL,) ^* [3 J% c1 c1 s# O* a2 l
which was clearly high. Some studies suggest that: i! z1 `9 y1 m
dermal conversion of testosterone to dihydrotestos-) k4 p n. X' f @. @
terone, which is a more potent metabolite, is more
# \! n* h" C* Z/ x! Bactive in young children exposed to testosterone
8 D$ D9 @) T$ U1 I! j* fexogenously7; however, we did not measure a dihy-
/ Z8 n$ K2 ~: [9 hdrotestosterone level in our patient. In addition to
5 C* k3 I# y, j: n+ q% Fvirilization, exposure to exogenous testosterone in
5 d% J* M) b; a: Q, h; E H) ?5 |# uchildren results in an increase in growth velocity and- e) b" E2 h% P7 x# ?
advanced bone age, as seen in our patient.5 j# R# G/ @/ Y' Z4 L
The long-term effect of androgen exposure during
$ T+ ~3 K' v* S% i: F. T. wearly childhood on pubertal development and final
* N" b0 i. k6 C# R4 f* B' A6 x+ cadult height are not fully known and always remain
" f" Q$ W" I8 M* Ya concern. Children treated with short-term testos-/ a4 V4 }" V8 R7 [9 |2 D a
terone injection or topical androgen may exhibit some2 m c9 B2 f1 D8 \7 B
acceleration of the skeletal maturation; however, after
; S2 \/ I5 S8 u: p, H4 hcessation of treatment, the rate of bone maturation
) }* U8 D9 F2 T) Z; edecelerates and gradually returns to normal.8,9
' _( ^' K+ k9 P a+ IThere are conflicting reports and controversy/ W D0 F/ e. |) T
over the effect of early androgen exposure on adult
2 a# R, s8 r+ J# T! qpenile length.10,11 Some reports suggest subnormal1 {- ~7 ~6 _3 ~ i: d9 V t, [
adult penile length, apparently because of downreg-
1 [4 b# Q% J! i+ Z Vulation of androgen receptor number.10,12 However,
+ l! u! X9 Q3 J4 w0 N3 F7 N0 ESutherland et al13 did not find a correlation between2 V( g) i$ \7 {& E
childhood testosterone exposure and reduced adult
7 v* Y' q; a5 I1 y- C" {. V+ ypenile length in clinical studies.
3 K8 {# j1 _6 ]Nonetheless, we do not believe our patient is
' o2 _! q: E- u, Zgoing to experience any of the untoward effects from( O( J- `$ Q# {" m% ~% N. E# P
testosterone exposure as mentioned earlier because j% I: P' N* K8 ]1 w8 H2 }; K }- z( b
the exposure was not for a prolonged period of time.' J: B- R/ L4 Z, E2 h5 k) {
Although the bone age was advanced at the time of
4 i( i. W. n% P8 cdiagnosis, the child had a normal growth velocity at ]3 D8 Q0 B7 M& B
the follow-up visit. It is hoped that his final adult
/ r7 T5 ^+ y% J+ l g8 z# l, Rheight will not be affected.& F2 E& Y$ k4 U& Z- x; R! U
Although rarely reported, the widespread avail-' a. y& v+ P; q, K7 C% I
ability of androgen products in our society may: k% y7 Z, a( V- q f& v
indeed cause more virilization in male or female
. z( f3 M2 Q, \) p$ E6 c8 R' Uchildren than one would realize. Exposure to andro-
- s& e) x: j9 ?0 fgen products must be considered and specific ques-
; f9 s8 d& ~, C, \tioning about the use of a testosterone product or- B4 K& U% t& S( b1 q Y8 g/ K$ K. x
gel should be asked of the family members during3 e6 M8 V1 F! |5 ~' t" l
the evaluation of any children who present with vir-3 O; m n# Q& m2 q/ s4 ^% F
ilization or peripheral precocious puberty. The diag-, k. @4 y5 G7 l# e
nosis can be established by just a few tests and by
! }- @" c$ k" n0 v- Aappropriate history. The inability to obtain such a |+ H' T, r7 n3 G& H) Z/ h3 |3 p% O
history, or failure to ask the specific questions, may
! n- l, `8 r2 v7 C6 Vresult in extensive, unnecessary, and expensive) b2 P2 q7 `6 J9 H* Q
investigation. The primary care physician should be1 l+ O; o9 |/ f* k9 Z% }+ n$ D
aware of this fact, because most of these children, ~, C- |7 H: X j& O* s
may initially present in their practice. The Physicians’
7 j: i: N2 c: Z, RDesk Reference and package insert should also put a7 i! ^1 G8 Y7 |& P3 J1 L' F9 m: }
warning about the virilizing effect on a male or+ M$ S/ v' t6 P$ n7 R& p. i
female child who might come in contact with some-
7 ^, n2 b0 i$ O0 F' None using any of these products.
D e, \* c! b: KReferences- N4 V, e- P! Q6 x
1. Styne DM. The testes: disorder of sexual differentiation# O' {! J- S* M0 L3 Q" h( N( Y u
and puberty in the male. In: Sperling MA, ed. Pediatric
4 D# Z$ ~' s! [' a$ Z& \1 UEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;8 i* E# X3 `7 N) y/ f0 t) \+ D5 H
2002: 565-628.! m2 i' A5 ~- G
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
# E' _# Y9 ?' npuberty in children with tumours of the suprasellar pineal |
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