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Sexual Precocity in a 16-Month-Old
, E6 k# F6 T" k+ @7 F2 bBoy Induced by Indirect Topical2 H5 V: f4 J- U6 ]: g! G
Exposure to Testosterone' V. f& ], _6 C3 P, U/ n$ r$ s
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2- ~9 b) M) Z: f$ y4 U, i! s- g) G% \
and Kenneth R. Rettig, MD1
( `/ M7 [- e' @Clinical Pediatrics1 W7 K, O% J. f. H
Volume 46 Number 6
/ x, J1 d ~# N7 r, }0 ?July 2007 540-543
) W6 d6 C( ?5 ?( w9 T© 2007 Sage Publications* s4 g; m7 E, h
10.1177/0009922806296651
+ h5 j0 Q; I& g& L5 O6 Yhttp://clp.sagepub.com; @" |7 s& F$ S" R' z. e2 e. I
hosted at
/ S3 M2 S, H) V) A9 Xhttp://online.sagepub.com, ]9 F; g# E3 S
Precocious puberty in boys, central or peripheral,( L4 N* A6 O6 U2 h
is a significant concern for physicians. Central! m, i5 U0 u% M- f, @9 H/ B
precocious puberty (CPP), which is mediated
* B- l6 R. ^; l6 B5 `4 |. rthrough the hypothalamic pituitary gonadal axis, has
4 w$ z5 [- ^5 q* Ga higher incidence of organic central nervous system3 k0 T1 [, }% l% y* |2 k
lesions in boys.1,2 Virilization in boys, as manifested
3 Z/ i. \! |3 t4 Y2 v8 Aby enlargement of the penis, development of pubic
' Z" }$ }. z5 G3 shair, and facial acne without enlargement of testi-
: {/ ^% m9 M% \) b% z2 ccles, suggests peripheral or pseudopuberty.1-3 We+ J% o, r6 }/ O8 q9 f3 ~# p
report a 16-month-old boy who presented with the
4 g4 Q% h6 Q1 k4 O8 }enlargement of the phallus and pubic hair develop-5 W$ `% R- I, R, {$ R6 t
ment without testicular enlargement, which was due7 V. H6 F4 z" `
to the unintentional exposure to androgen gel used by
: U6 e9 {; ^5 t; u* R$ \2 v$ n4 q& othe father. The family initially concealed this infor-
$ y% _0 q8 T- e7 k) L1 fmation, resulting in an extensive work-up for this$ C1 Q& Z0 F" d# f2 t/ a
child. Given the widespread and easy availability of( ^! S+ e+ ^7 ^2 `
testosterone gel and cream, we believe this is proba-
6 s. l% s# ^5 X# e7 k. h- Tbly more common than the rare case report in the
2 N S0 Z& G6 e |1 hliterature.4
, e! z" \1 g2 iPatient Report
, z) B5 \% r, K8 T GA 16-month-old white child was referred to the
6 I: K) K5 L; Q& P5 f3 H Aendocrine clinic by his pediatrician with the concern
$ ^8 _8 a2 g% @of early sexual development. His mother noticed
: m$ x3 I( n5 q! @! `light colored pubic hair development when he was
0 `" B/ @% p$ NFrom the 1Division of Pediatric Endocrinology, 2University of; M/ L# ?& b% V, G2 E! x
South Alabama Medical Center, Mobile, Alabama.$ \- s) g+ a4 k7 t1 z: X+ g' F
Address correspondence to: Samar K. Bhowmick, MD, FACE,; R3 M5 g' Z- M
Professor of Pediatrics, University of South Alabama, College of3 s) F* @& P f m1 z
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
9 ]3 h9 o; `4 Ge-mail: [email protected].) ?0 K3 V! M& H" U" A$ B( ^" {
about 6 to 7 months old, which progressively became
# D% V2 F5 U5 ~( ]3 o/ `3 ?( u# }: ?darker. She was also concerned about the enlarge-+ Z$ J0 P- T1 h( G3 ]
ment of his penis and frequent erections. The child
. O3 [! U( s' {+ y2 Uwas the product of a full-term normal delivery, with" U) H0 S9 ^5 @" s
a birth weight of 7 lb 14 oz, and birth length of
8 V/ L" F" M* N( j2 W8 G20 inches. He was breast-fed throughout the first year
- X6 t3 e# g7 \3 O4 B& u4 |of life and was still receiving breast milk along with& M0 _; m9 e: z* r( W9 C+ _& s' w& Q
solid food. He had no hospitalizations or surgery,
4 A$ T" a9 n6 V8 C- band his psychosocial and psychomotor development
! I6 ]0 ]8 Q# t. r+ u0 ?was age appropriate.
. a! J: {+ Y& j4 V" eThe family history was remarkable for the father,
: B, V' E+ R+ ~' h0 Y* b% _5 Swho was diagnosed with hypothyroidism at age 16,
% ~0 s( F, Q, k5 U: Y$ v, Jwhich was treated with thyroxine. The father’s+ n. X, p, s& M& G
height was 6 feet, and he went through a somewhat
# u) p W7 V9 P2 Uearly puberty and had stopped growing by age 14.& m, S4 Z- F) e' c9 F
The father denied taking any other medication. The, u1 f* v" l, B6 i% {. _
child’s mother was in good health. Her menarche
2 N/ j( x% n' F, G, cwas at 11 years of age, and her height was at 5 feet- |1 F, ]0 h5 I7 s0 J
5 inches. There was no other family history of pre-, v! a: M) `* ~; F- k
cocious sexual development in the first-degree rela-
1 Q% n' P$ o+ R' B" [tives. There were no siblings.
! a6 a% M1 R- [/ iPhysical Examination
& Q/ z0 e; r0 s( b7 y- e* O- I2 OThe physical examination revealed a very active,1 o- g$ a" _$ q7 v' z( M; ?
playful, and healthy boy. The vital signs documented
. u" s) Z8 A4 k8 E5 j9 }; ja blood pressure of 85/50 mm Hg, his length was' _5 l/ v6 @- q a1 l
90 cm (>97th percentile), and his weight was 14.4 kg
# k& S) C) w0 s: F$ W(also >97th percentile). The observed yearly growth8 u, {. e& j) n8 m; s' i
velocity was 30 cm (12 inches). The examination of& C- [5 n w( A% e3 z+ O
the neck revealed no thyroid enlargement.
/ q2 T0 V H% I+ M8 Y! \The genitourinary examination was remarkable for" r, b7 B$ P/ d" g1 G9 K
enlargement of the penis, with a stretched length of9 X( N2 |3 J# ]
8 cm and a width of 2 cm. The glans penis was very well
+ w! o2 }, ^; d/ x" W6 I8 v [- zdeveloped. The pubic hair was Tanner II, mostly around
; l2 l, |8 f# p4 F540/ }; T- j! q& ~: _2 G
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from1 R+ {! W6 z- e& @7 t0 _! M) v
the base of the phallus and was dark and curled. The! b5 u% Q; z" q. A! h" |6 w8 R
testicular volume was prepubertal at 2 mL each.
) F' N2 ?3 I$ | @The skin was moist and smooth and somewhat; d, n/ ? r5 b0 Q0 F; g
oily. No axillary hair was noted. There were no7 o5 q- v$ n7 I% S
abnormal skin pigmentations or café-au-lait spots.
- }& \9 k1 d& o/ z# ?Neurologic evaluation showed deep tendon reflex 2+
9 {6 g! l0 S+ Q+ D9 f+ Bbilateral and symmetrical. There was no suggestion" y' B8 F9 ^, F
of papilledema.3 U2 D K* |; k) w! a! M* P; u0 U
Laboratory Evaluation# z7 } y7 V- ~: n
The bone age was consistent with 28 months by5 `9 w. X, f1 a+ E" N
using the standard of Greulich and Pyle at a chrono-
- i5 h" N5 a9 W9 g' E. Llogic age of 16 months (advanced).5 Chromosomal# P, O& u3 }+ T$ Q" z9 M: C
karyotype was 46XY. The thyroid function test, R! ]8 T1 s6 I' ~, O+ c
showed a free T4 of 1.69 ng/dL, and thyroid stimu-
' j! C$ X, f9 [' L/ N( blating hormone level was 1.3 µIU/mL (both normal).8 J) j: B: h V7 I3 l$ h
The concentrations of serum electrolytes, blood; R. s+ U8 z7 P6 Y
urea nitrogen, creatinine, and calcium all were
# A& A+ z% G0 |within normal range for his age. The concentration/ H4 D7 V7 @# _4 ]6 |6 ^
of serum 17-hydroxyprogesterone was 16 ng/dL+ z0 U& k. c' K& P: w7 K: d
(normal, 3 to 90 ng/dL), androstenedione was 20
$ z0 I7 b5 P7 Q' C4 T- ?; Bng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-" i0 V/ V2 }6 z9 {& |! s A
terone was 38 ng/dL (normal, 50 to 760 ng/dL),
) k9 _9 q# |0 Wdesoxycorticosterone was 4.3 ng/dL (normal, 7 to/ @' y o- [( {6 x1 l+ [1 i3 t% R
49ng/dL), 11-desoxycortisol (specific compound S)
7 I8 w& ~6 F% {! v% q! Kwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
* E# T9 @" x( s7 g$ F2 j7 A- @tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
) b/ g- ~6 s$ y/ G6 G" qtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
$ J( _. H! M: n9 Yand β-human chorionic gonadotropin was less than
1 Y3 o, d9 V! H, z$ a. t2 U) M% U5 mIU/mL (normal <5 mIU/mL). Serum follicular& [3 X/ {! i# v: g! n% R
stimulating hormone and leuteinizing hormone
3 Y$ m8 [ S* D9 tconcentrations were less than 0.05 mIU/mL! \* D7 Y0 c( n& B5 d3 J
(prepubertal).+ i! m1 \1 x# ~- e/ I' M6 c
The parents were notified about the laboratory
! O$ h& K6 A4 Tresults and were informed that all of the tests were
4 q0 I8 g, p dnormal except the testosterone level was high. The' x! u% f4 F$ k- d& y7 l# x
follow-up visit was arranged within a few weeks to
+ v- ^3 G& J9 Z: c4 H; d# o( [obtain testicular and abdominal sonograms; how-( s$ [' m4 ]8 Z7 y: j5 O4 n" K
ever, the family did not return for 4 months.+ q1 y& A3 [( I. J( C0 U
Physical examination at this time revealed that the/ r3 R, C8 g3 E9 R0 z' |$ \1 R
child had grown 2.5 cm in 4 months and had gained
. F2 N3 J/ _3 r" R+ b3 W2 kg of weight. Physical examination remained
9 m, O& r" l9 Y; v+ L' Punchanged. Surprisingly, the pubic hair almost com-0 n M8 ~! l5 S( I) k
pletely disappeared except for a few vellous hairs at
2 S1 q) J8 e9 `7 Jthe base of the phallus. Testicular volume was still 2
! |9 v+ }. [# z1 O' g5 C. d! H. c8 `) ImL, and the size of the penis remained unchanged.- {/ E* M3 H/ J: y; i0 _! K
The mother also said that the boy was no longer hav-+ X/ B0 g- h e0 O2 s% k
ing frequent erections.* ? } s1 j1 V% ~) v9 d+ P: w) p
Both parents were again questioned about use of
/ h* r" e ^4 `5 h5 Oany ointment/creams that they may have applied to
9 l& {, u. S, v1 R4 dthe child’s skin. This time the father admitted the, K; ^5 ?# r) T
Topical Testosterone Exposure / Bhowmick et al 541
, u8 c7 l/ A0 f! ]" O2 `use of testosterone gel twice daily that he was apply-! Y* @1 m1 }+ ?
ing over his own shoulders, chest, and back area for, z( \1 q! E. N+ }
a year. The father also revealed he was embarrassed
& {( x: i1 H" c' a& sto disclose that he was using a testosterone gel pre-! S6 N% @7 ~: S j( {: c3 x
scribed by his family physician for decreased libido
" U' C8 @ f. esecondary to depression.8 {+ `/ V1 l$ C# t8 I! h6 r' x
The child slept in the same bed with parents.
2 N+ A9 o% p% Z$ m* F* p# c& jThe father would hug the baby and hold him on his5 S+ B! q# w/ [( f
chest for a considerable period of time, causing sig-
' e5 g3 w2 e/ z# Hnificant bare skin contact between baby and father.! X5 g" m! e6 k% l2 s" s
The father also admitted that after the phone call,
: k6 ~. r0 E$ q% T: dwhen he learned the testosterone level in the baby
1 |- \& s' N+ Q- q! ]was high, he then read the product information
- O. r/ W n& o T' \8 \# r- u/ Ypacket and concluded that it was most likely the rea-/ E5 x1 b+ X0 N; B+ f! S/ N' \
son for the child’s virilization. At that time, they
( v, S/ p% w4 M! O9 O* Udecided to put the baby in a separate bed, and the: c7 \# v4 u6 X0 c( |) }( u
father was not hugging him with bare skin and had: @9 H: z* L& \ B. c4 W
been using protective clothing. A repeat testosterone
6 u! H. u, Q; C# T; Y# ?2 Ctest was ordered, but the family did not go to the* ^7 }" m+ V; L' _4 {$ c, B
laboratory to obtain the test.2 A9 }! `! b0 b' C6 j
Discussion
1 \( `2 x* F% d A" p" L! XPrecocious puberty in boys is defined as secondary
( { q9 `; j9 r/ }% v) m. J, B3 D* Hsexual development before 9 years of age.1,40 b! l) C& _0 E0 \4 U: N( k7 @
Precocious puberty is termed as central (true) when3 [3 o3 U' x7 ^8 L/ [6 @
it is caused by the premature activation of hypo-
# i# c6 x5 j T2 o6 ?" A: \* Othalamic pituitary gonadal axis. CPP is more com-
' ^: s! P& L9 |: T& Xmon in girls than in boys.1,3 Most boys with CPP) F ? Y" g6 L) G) u* d
may have a central nervous system lesion that is
0 M8 D" [" y# ]6 u* eresponsible for the early activation of the hypothal-/ {1 P G. e; M! s" S# ]9 U
amic pituitary gonadal axis.1-3 Thus, greater empha-, P- q5 M; J' Z1 d e/ E
sis has been given to neuroradiologic imaging in
' h* a9 ~0 f1 y: v; z/ Z8 f% W9 Z uboys with precocious puberty. In addition to viril-
# x8 J- H% u' V& k' h# mization, the clinical hallmark of CPP is the symmet-0 z; W, r& t1 i# V
rical testicular growth secondary to stimulation by
1 a7 I) z; `' V8 x/ {) Zgonadotropins.1,3' r8 X# r; Y) J9 J8 r# P2 f2 j
Gonadotropin-independent peripheral preco-1 ^+ H1 n2 A. @/ t! r
cious puberty in boys also results from inappropriate8 M4 d6 z' _' ]
androgenic stimulation from either endogenous or
5 C7 y& E. a1 f9 [ [3 [* m8 f1 k: Iexogenous sources, nonpituitary gonadotropin stim-
7 R5 j y6 L7 W+ A. culation, and rare activating mutations.3 Virilizing
7 G+ s9 K& T% f: ~) N1 G/ `5 e1 dcongenital adrenal hyperplasia producing excessive
* I S* T6 h- l1 zadrenal androgens is a common cause of precocious
% m' s- k4 P$ n" l0 r* |puberty in boys.3,4
# }2 H" x7 S0 [5 p' z3 Z! ?The most common form of congenital adrenal; F+ u. F+ V- V+ ^6 l; p/ e
hyperplasia is the 21-hydroxylase enzyme deficiency.
8 _$ {! ], U4 OThe 11-β hydroxylase deficiency may also result in3 ]6 J2 B# @7 ^( a- g1 s
excessive adrenal androgen production, and rarely,% ~! x! h% \* S$ A8 i- q
an adrenal tumor may also cause adrenal androgen
& ] \3 i" W2 t# L# D1 N0 [excess.1,3$ M! x" Q: ^' t* O
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
1 s1 {3 ^. |0 E: Y/ l6 b0 Z542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
! Z7 A. P/ T4 A- b n6 W( TA unique entity of male-limited gonadotropin-8 b+ U( O; k8 |( V6 r, L. k3 {# {9 @
independent precocious puberty, which is also known
8 e/ d% C4 N: \* f. i! Tas testotoxicosis, may cause precocious puberty at a- i- Z/ Y+ @" u5 c3 U+ n/ z! T5 H
very young age. The physical findings in these boys
) h( m; T# v4 R3 I3 _, P9 M" Z5 gwith this disorder are full pubertal development,$ I1 c, g7 m, R& _& o7 T
including bilateral testicular growth, similar to boys; p9 q# [4 L' k' \
with CPP. The gonadotropin levels in this disorder1 r1 K) S% \* { {1 W+ M
are suppressed to prepubertal levels and do not show
2 D3 h) y/ M1 X+ A, Gpubertal response of gonadotropin after gonadotropin-: @. d: Q1 @ y4 M8 W
releasing hormone stimulation. This is a sex-linked- o: V& V. f/ x2 \' E- ~
autosomal dominant disorder that affects only
9 b* S0 {1 r. W5 A6 umales; therefore, other male members of the family
/ g- M1 A" [. }& @# n5 Pmay have similar precocious puberty.3( A, c$ [# D' B0 w3 Q- @ V
In our patient, physical examination was incon-
2 E1 R* X# k8 n* t Q( rsistent with true precocious puberty since his testi-
3 w; D" A4 Q3 d1 q2 U1 vcles were prepubertal in size. However, testotoxicosis
0 F6 ]- v4 r. E. Ewas in the differential diagnosis because his father
. R, K5 H, ^- D8 s( f. V tstarted puberty somewhat early, and occasionally,( Z" N: `" }0 T" R/ k2 j& a
testicular enlargement is not that evident in the6 h+ V' n0 {; p6 Z. J' J/ ^8 W% }
beginning of this process.1 In the absence of a neg-
4 w p7 z; w7 b4 O' K! g) {ative initial history of androgen exposure, our
1 X6 ?1 x% Y$ `% jbiggest concern was virilizing adrenal hyperplasia,
. `4 N# B+ u0 @either 21-hydroxylase deficiency or 11-β hydroxylase
5 A5 X* e; f& F( Z- G* \& D' udeficiency. Those diagnoses were excluded by find-& w; y$ M3 R$ f0 n+ r
ing the normal level of adrenal steroids.3 q* s5 p* c3 w3 X8 j& F& {' w
The diagnosis of exogenous androgens was strongly, r- g7 O0 F# X* `7 v$ U
suspected in a follow-up visit after 4 months because( n) K3 P4 K/ [4 Y# P
the physical examination revealed the complete disap-! C0 P- q7 @, X/ ^7 P' [8 e
pearance of pubic hair, normal growth velocity, and4 |' J- F: A" q8 M# Y0 T2 T8 W
decreased erections. The father admitted using a testos-8 @& o/ y2 u" _) R/ d
terone gel, which he concealed at first visit. He was% j5 h. ?' Z! q1 g: a
using it rather frequently, twice a day. The Physicians’3 f, f. D$ D' [1 b
Desk Reference, or package insert of this product, gel or+ f1 g$ b% T% l9 v3 i4 x
cream, cautions about dermal testosterone transfer to
; d' h8 x( x9 P* |unprotected females through direct skin exposure.8 _% B6 ~& v. h; }
Serum testosterone level was found to be 2 times the
* T) c: x1 ]0 fbaseline value in those females who were exposed to' N6 d- ]" Z# H9 Q
even 15 minutes of direct skin contact with their male. ?! M. J4 V! _
partners.6 However, when a shirt covered the applica-5 b. u( |7 _! F3 F9 m; ?
tion site, this testosterone transfer was prevented. }( v r8 A5 u
Our patient’s testosterone level was 60 ng/mL,
# Q3 I' v& M1 o4 ewhich was clearly high. Some studies suggest that
1 s/ h) Y" ]. hdermal conversion of testosterone to dihydrotestos-* P+ ^: ^' N( b! Y7 \# C% S
terone, which is a more potent metabolite, is more& Y m1 [* J2 v% f! ?3 z# Y
active in young children exposed to testosterone
' D% ?; M5 q- O0 O3 {+ D3 texogenously7; however, we did not measure a dihy-
- x' f8 I3 t5 b+ `) _2 D) `4 ddrotestosterone level in our patient. In addition to" z2 c3 _$ p: m8 r s; s
virilization, exposure to exogenous testosterone in
* v8 j2 l3 Z' v$ ]6 Pchildren results in an increase in growth velocity and
8 p2 Y& v3 C3 s3 b( z, F2 Wadvanced bone age, as seen in our patient.' C. H( \6 h5 q1 Y
The long-term effect of androgen exposure during7 Y D1 q/ v v1 i; m6 w P
early childhood on pubertal development and final0 V: U2 ?* V. r$ Y, G& E C7 i
adult height are not fully known and always remain
4 I$ ^" e) _0 Ha concern. Children treated with short-term testos-
% r* M) S) |% Q4 Pterone injection or topical androgen may exhibit some9 Q+ k* c+ `0 w9 ~ o6 v
acceleration of the skeletal maturation; however, after2 B$ C; ^' q0 `2 f+ _! s
cessation of treatment, the rate of bone maturation$ ~9 `. f. i: t7 x7 o/ Q
decelerates and gradually returns to normal.8,99 o. c+ g$ R5 F
There are conflicting reports and controversy( S% [/ e4 [9 ?1 `( R# x+ J
over the effect of early androgen exposure on adult! O( Y& e( [( y) n1 \6 O1 W
penile length.10,11 Some reports suggest subnormal
+ T1 h# t+ p0 J4 b+ G g$ _adult penile length, apparently because of downreg-/ R$ P% \! g8 P E& B
ulation of androgen receptor number.10,12 However,/ s3 ~0 a) A' O
Sutherland et al13 did not find a correlation between( @2 w9 @5 j- w! E
childhood testosterone exposure and reduced adult! U' P; b' q9 x3 X: D: z8 {
penile length in clinical studies.
3 L6 L+ r7 z9 N, ~$ a) y8 ~Nonetheless, we do not believe our patient is
! ?. X: k1 {% W5 ]3 v. ]going to experience any of the untoward effects from
2 [; x" @ |5 g8 |* gtestosterone exposure as mentioned earlier because
# p3 V. i8 b9 m$ lthe exposure was not for a prolonged period of time.
+ X0 w0 w* S% o; _- A rAlthough the bone age was advanced at the time of
1 n J k1 L" o& j& Adiagnosis, the child had a normal growth velocity at
# F y- x: J2 J" L( bthe follow-up visit. It is hoped that his final adult# R: B& h( B2 H- \' C8 T% ]
height will not be affected.
5 h% J' S0 k; D" |/ v% b0 ]Although rarely reported, the widespread avail-
: w" k- e+ j& {: R6 O: }- |& h/ ]8 Xability of androgen products in our society may) P- w5 i" N v
indeed cause more virilization in male or female
: K* A' E- k( }0 Kchildren than one would realize. Exposure to andro-
# n5 I8 s" }4 J* }# wgen products must be considered and specific ques-" m; l1 \2 a- e( k' d. ^ Y# W
tioning about the use of a testosterone product or. o; V2 B u' i' v$ y5 c, f; `
gel should be asked of the family members during* i g9 G! Q: G2 Z8 \2 x
the evaluation of any children who present with vir-9 N' e5 n% U; ~6 [; v1 T2 ~$ p
ilization or peripheral precocious puberty. The diag-' k# P# G6 h& ?1 t6 g7 D6 T* q
nosis can be established by just a few tests and by+ A* ]9 e9 v+ [7 O$ u) f( u1 D
appropriate history. The inability to obtain such a
+ G# V0 K; [' H) Lhistory, or failure to ask the specific questions, may
' Y& r5 x6 R! l( z- k. ~' {result in extensive, unnecessary, and expensive0 v; v) w# y. v" T
investigation. The primary care physician should be
+ g4 c* f6 H2 i D% ? P! B& s( O; Gaware of this fact, because most of these children: j! @ P% {& `. O6 C# Z- r
may initially present in their practice. The Physicians’
0 _* `+ j1 B- w! \5 {1 d6 PDesk Reference and package insert should also put a
3 w* n! w, b7 W4 F1 }. |warning about the virilizing effect on a male or+ a8 I y) h1 u6 @2 d
female child who might come in contact with some-+ [* j; q* l/ e$ _& Z, ?1 B% I
one using any of these products.! Z+ K5 O% V5 h* {- R9 Y& X8 K8 I* J* @
References
- O+ t/ Y$ v1 l5 E, @5 e4 K1. Styne DM. The testes: disorder of sexual differentiation! B$ X' \$ u3 v" l1 [
and puberty in the male. In: Sperling MA, ed. Pediatric7 a* G6 p, t) U
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;7 ]3 X1 K! @& G) g! `" k
2002: 565-628.
$ m$ x0 N) R' d2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
# B! v+ {1 W! G; F# Mpuberty in children with tumours of the suprasellar pineal |
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