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Sexual Precocity in a 16-Month-Old
0 H% Z, G T9 o+ `* X0 eBoy Induced by Indirect Topical* B( ?; v* v; Y
Exposure to Testosterone
: i! o$ N3 k2 PSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2$ ?" D: g6 Y6 Q& @
and Kenneth R. Rettig, MD1* G: x, @$ m8 a$ j+ h* O; {
Clinical Pediatrics
* j5 L6 k$ @. T: c% HVolume 46 Number 6
: i, O: U0 W) i6 k: q5 e% AJuly 2007 540-543
6 Z0 l. i# Q8 [1 i P© 2007 Sage Publications# r) e& e7 {4 Q, ?
10.1177/0009922806296651
+ P) {" h/ Y3 K/ S0 khttp://clp.sagepub.com
1 L8 `! l& I2 m- l: ]hosted at
6 U' d5 u6 X8 S5 m$ B0 L( khttp://online.sagepub.com
5 B9 C$ a1 z( p% BPrecocious puberty in boys, central or peripheral,: u4 j" v0 I8 ~# T
is a significant concern for physicians. Central
% [: c: I1 |2 ~4 u) w, pprecocious puberty (CPP), which is mediated5 B$ V! u2 {/ V3 I
through the hypothalamic pituitary gonadal axis, has
- G- q% p8 V& ha higher incidence of organic central nervous system
) c; N( @9 _2 g3 Ulesions in boys.1,2 Virilization in boys, as manifested
* w* f# U/ [6 o2 F- K9 F" wby enlargement of the penis, development of pubic
" m w! {) ]& X8 P4 Chair, and facial acne without enlargement of testi-
! {+ {4 r6 x+ k3 |! P- |3 vcles, suggests peripheral or pseudopuberty.1-3 We7 V( [6 v( U5 `( I }, [
report a 16-month-old boy who presented with the
4 M# |- P7 ^. `7 w' ^" senlargement of the phallus and pubic hair develop-
6 j" A/ G. U4 ^. `' ?/ yment without testicular enlargement, which was due, r" {+ N/ W' o7 m1 t) h/ u! Y8 j$ h
to the unintentional exposure to androgen gel used by# D( |8 i/ O2 A6 N" g& L" b
the father. The family initially concealed this infor-
# t8 X( O3 Y# P) e3 A X6 c% F. v8 Vmation, resulting in an extensive work-up for this
# y0 z; S; C- s; }$ c, ^) o% Schild. Given the widespread and easy availability of T" B' h$ c1 V6 C! b
testosterone gel and cream, we believe this is proba-% ^4 P5 D; H7 r: @0 z
bly more common than the rare case report in the
" c7 k8 _- x4 ?/ q/ xliterature.4* Y/ _6 v3 q1 T- S' o7 {
Patient Report
( L; g" H0 A! p* FA 16-month-old white child was referred to the
9 ~' T, y( i# i% jendocrine clinic by his pediatrician with the concern
3 X! _* U% {/ }of early sexual development. His mother noticed. U3 n5 w7 b& o, ?5 d8 V$ F2 L
light colored pubic hair development when he was) f" e/ Q) R. Y; d: I, B+ ]
From the 1Division of Pediatric Endocrinology, 2University of% n* c0 W- W1 j* N# G
South Alabama Medical Center, Mobile, Alabama.
% o# Z) X6 g; t/ bAddress correspondence to: Samar K. Bhowmick, MD, FACE,; |3 q. ?3 Y* l2 F
Professor of Pediatrics, University of South Alabama, College of7 b7 z S) G, g3 x- e/ B" c1 N
Medicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;( {& d, `; L. H; k) j7 O. `
e-mail: [email protected].9 f- V7 n0 T# u; C/ ]
about 6 to 7 months old, which progressively became
4 U# P6 B' O: s. y, V; i: [darker. She was also concerned about the enlarge-
3 O& a( t% o5 ~7 [1 u0 ]ment of his penis and frequent erections. The child
1 f( Z8 I, F$ |% e. Wwas the product of a full-term normal delivery, with
0 Y- {: E+ P# p S- m0 E! Ha birth weight of 7 lb 14 oz, and birth length of; [: Q. ?- ^* _9 L8 z' \9 Y: {
20 inches. He was breast-fed throughout the first year
$ d" x6 \; `5 I& x" N5 Nof life and was still receiving breast milk along with( Z7 ] S& G+ c8 h! @+ t7 p3 e
solid food. He had no hospitalizations or surgery,) U6 Y; k! t" F" Z" k, Z1 ^3 r+ Z. U
and his psychosocial and psychomotor development& k0 x) y: n9 m8 \3 f
was age appropriate.: ]% e4 o4 D( o# f/ E% O# L
The family history was remarkable for the father,
) v2 W% f9 }: ~7 i5 C- hwho was diagnosed with hypothyroidism at age 16,
# k6 e2 W8 D, c Twhich was treated with thyroxine. The father’s
6 d! O1 c2 P q( N7 Q) sheight was 6 feet, and he went through a somewhat! i+ `5 B, O$ B) d
early puberty and had stopped growing by age 14.
, U0 s9 J0 q( j- h6 L7 L$ W+ CThe father denied taking any other medication. The5 B( C( y/ V- }0 S; ~# x1 {. q
child’s mother was in good health. Her menarche
7 c% d# [' o) i6 zwas at 11 years of age, and her height was at 5 feet& ?# Q+ E F. b" Y
5 inches. There was no other family history of pre-0 O% F" F( _- c0 j- P) K
cocious sexual development in the first-degree rela-. n% s! `" s0 Z
tives. There were no siblings.
N6 a& V- Y: N& P2 x& P0 \7 zPhysical Examination
& n6 L: {$ T& z" V q$ N- O* DThe physical examination revealed a very active,
$ n" u. ^; m0 ^+ Z* Xplayful, and healthy boy. The vital signs documented* I' q! s' J; C* p2 V) d% ^
a blood pressure of 85/50 mm Hg, his length was! w" l9 \+ F* a7 r: g1 C
90 cm (>97th percentile), and his weight was 14.4 kg2 d9 a/ K' \, U
(also >97th percentile). The observed yearly growth/ d. X) |0 ?2 F# W1 T5 C
velocity was 30 cm (12 inches). The examination of
' T0 ^. [3 Y( _2 Nthe neck revealed no thyroid enlargement.
. q1 V, k2 ^. ^" }5 TThe genitourinary examination was remarkable for
# Q1 a# r+ j7 kenlargement of the penis, with a stretched length of! \2 N+ A: p# G2 V! c, z
8 cm and a width of 2 cm. The glans penis was very well
! Q* }& E- U% J: M( Vdeveloped. The pubic hair was Tanner II, mostly around
2 z& d6 u; x, {4 i540
) \) Y9 U2 m5 I6 M$ Gat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from- j1 }& y2 a( O2 `
the base of the phallus and was dark and curled. The
/ s% E# T H5 otesticular volume was prepubertal at 2 mL each.. X4 n1 K. Y# P# F& E& K% d
The skin was moist and smooth and somewhat7 V) N) }5 c. Q) x3 E, f9 W
oily. No axillary hair was noted. There were no
1 U6 E3 h% t1 F( uabnormal skin pigmentations or café-au-lait spots.
* v6 W" v6 d' \; ~: `- } t zNeurologic evaluation showed deep tendon reflex 2+" M1 L, v9 |% U. m
bilateral and symmetrical. There was no suggestion; g' Z) M5 e& N
of papilledema.7 b) A" l- P4 `. X
Laboratory Evaluation
. H3 o% Z- j" I# q/ P0 J3 NThe bone age was consistent with 28 months by
, c6 y0 z% x! s" q; zusing the standard of Greulich and Pyle at a chrono-6 ? R) l$ b7 c, u
logic age of 16 months (advanced).5 Chromosomal
& l. J, u1 h8 c f1 L8 dkaryotype was 46XY. The thyroid function test; @: L* O; H5 W2 E) g6 o* X% L
showed a free T4 of 1.69 ng/dL, and thyroid stimu-* b6 ^, u. f" v8 y2 }2 A; J; }
lating hormone level was 1.3 µIU/mL (both normal).# W# w/ \: I' N- J
The concentrations of serum electrolytes, blood
& o# E$ j1 M. P7 B1 L) iurea nitrogen, creatinine, and calcium all were/ [* B; y+ w; u% c3 y0 `, n8 \3 e
within normal range for his age. The concentration
. \ b3 ]5 c8 ^" l: s; Uof serum 17-hydroxyprogesterone was 16 ng/dL" ?7 \- N3 D" K! V) j
(normal, 3 to 90 ng/dL), androstenedione was 20
( x6 \ P1 D5 i8 M7 ung/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
* |; l( O2 U" T! O* S. O1 \% xterone was 38 ng/dL (normal, 50 to 760 ng/dL),6 F; g% \. |; G' [% X: `" y- N6 y
desoxycorticosterone was 4.3 ng/dL (normal, 7 to: G$ W* l; _6 F# x5 c! n
49ng/dL), 11-desoxycortisol (specific compound S)2 s# D1 p! K+ x& C" q" W' y
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
9 P$ Y3 m; P# f! h) O( V% ztisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
- p8 @1 K/ K( R7 Ltestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
( ?' W& J* y& v, j- a6 ]7 Yand β-human chorionic gonadotropin was less than
+ M3 u+ v5 ^& M9 o- ]4 ]' J7 V5 U5 mIU/mL (normal <5 mIU/mL). Serum follicular
, N. }; K6 i1 Bstimulating hormone and leuteinizing hormone
q! U/ K# h, l# jconcentrations were less than 0.05 mIU/mL
8 _. X1 [3 \+ q) o: h4 }(prepubertal).# H/ v& c; ~3 {, i6 v4 ?. G; S
The parents were notified about the laboratory1 g" O( k" I7 C+ Z4 l: n/ @% y6 R7 U
results and were informed that all of the tests were6 q7 t) p$ c: m) r( P9 W5 H% ]6 v
normal except the testosterone level was high. The2 N. n* _5 K2 c5 f
follow-up visit was arranged within a few weeks to7 k/ c8 y$ u2 }" ]
obtain testicular and abdominal sonograms; how-
2 F; |6 h$ g$ g7 d3 [& A+ I" wever, the family did not return for 4 months.
4 ]+ V) H$ A4 b: y5 b6 D) JPhysical examination at this time revealed that the; ~1 q/ ~) ?8 c2 d6 q9 u
child had grown 2.5 cm in 4 months and had gained% F' p- L3 M8 q) v' O5 g
2 kg of weight. Physical examination remained) k n2 J: N+ e. v
unchanged. Surprisingly, the pubic hair almost com-1 C" A/ c/ \- R* T i1 j/ h
pletely disappeared except for a few vellous hairs at
& b- O9 J- L- P7 h+ }/ wthe base of the phallus. Testicular volume was still 2; R6 |0 W7 S% e/ S/ O
mL, and the size of the penis remained unchanged.
6 M2 ~0 U, \2 Q U! b; ]% YThe mother also said that the boy was no longer hav-$ A7 t. U3 |) d" s+ R
ing frequent erections.
% c2 L7 F6 T- R2 F& c7 ]+ B' O2 eBoth parents were again questioned about use of+ F2 Z& R8 V2 z2 T: x
any ointment/creams that they may have applied to
2 N% }0 }, F3 c/ E& ?8 n" ethe child’s skin. This time the father admitted the$ Z3 @* _+ q3 E" ~- d
Topical Testosterone Exposure / Bhowmick et al 5419 Q; r% k+ x% t! a- ]
use of testosterone gel twice daily that he was apply-$ ]; m- O& n9 J2 Q% V
ing over his own shoulders, chest, and back area for
. A+ U( S _* O& ]/ w% ya year. The father also revealed he was embarrassed% V! `& a- E* O$ B& F
to disclose that he was using a testosterone gel pre-
+ f! ^, [# n+ @/ `/ P7 Bscribed by his family physician for decreased libido
! i8 L- \8 h! A Y. b8 Dsecondary to depression.9 t' f/ X" v4 U# ^. c
The child slept in the same bed with parents.% V# b7 L& w, D& m- d; X! H3 Y/ L/ C
The father would hug the baby and hold him on his4 ^4 q( f" l8 }# \
chest for a considerable period of time, causing sig-
# F" N" I% X3 nnificant bare skin contact between baby and father.6 l) _7 ]9 n4 H2 @) K
The father also admitted that after the phone call,* d/ z4 n R$ G) e5 w6 F0 z+ G
when he learned the testosterone level in the baby8 Y7 x- @8 H& S, e
was high, he then read the product information
& L: b6 F* ?% G, j% W1 D H! p) }packet and concluded that it was most likely the rea-
0 {1 a+ L% l# a5 Xson for the child’s virilization. At that time, they
7 h* @1 q/ F2 Z- k/ {$ O3 f1 _decided to put the baby in a separate bed, and the* U' S9 A+ W/ `8 Z9 g3 c
father was not hugging him with bare skin and had
) J6 E4 E3 V' u J5 g7 r; e7 Kbeen using protective clothing. A repeat testosterone
% p V. b6 Z7 M/ utest was ordered, but the family did not go to the
* \4 T! ^; t5 S0 i) v3 f3 }- ]laboratory to obtain the test.
* z% O3 S+ R2 ~8 H7 R j8 N2 PDiscussion
$ K1 Q# P0 w! f+ G8 B' qPrecocious puberty in boys is defined as secondary& N- k. O4 M' h! {5 u" H$ P
sexual development before 9 years of age.1,4
1 A* u* p# d, n' cPrecocious puberty is termed as central (true) when( O6 w$ F8 j7 w. ]1 S
it is caused by the premature activation of hypo-: E% K' i% \( n. h' @, `7 a
thalamic pituitary gonadal axis. CPP is more com-
* H# ~; L% g1 P8 R, Umon in girls than in boys.1,3 Most boys with CPP
% ?0 F W) I) v2 H+ amay have a central nervous system lesion that is) |. D0 @, }% w1 G& O6 R' r
responsible for the early activation of the hypothal-
; m( V2 M7 Y6 W, ] ], Pamic pituitary gonadal axis.1-3 Thus, greater empha-$ f, v1 a* _4 n: \+ N' Z, s
sis has been given to neuroradiologic imaging in+ ?6 k5 x* C) E! C- W& U/ _
boys with precocious puberty. In addition to viril-
0 u5 B; f' \* H, A$ Vization, the clinical hallmark of CPP is the symmet-
) l+ O6 Q ^) f- h$ hrical testicular growth secondary to stimulation by7 L; q& ?. Z4 d' s
gonadotropins.1,30 {+ Q* ?1 C3 E! r/ |* N/ l
Gonadotropin-independent peripheral preco-
7 ~# A) {% D! C0 F. @6 x3 Rcious puberty in boys also results from inappropriate
4 y/ e4 u: [1 _ n, Randrogenic stimulation from either endogenous or
7 Z2 R' L8 i; F" o9 |4 kexogenous sources, nonpituitary gonadotropin stim-
& p0 f6 M8 J( w0 K' tulation, and rare activating mutations.3 Virilizing/ h7 s( Q, l% R2 Y1 c8 R+ P9 m& C; k
congenital adrenal hyperplasia producing excessive, |# G/ N! g! z
adrenal androgens is a common cause of precocious6 w- f$ W* ]( Q' P
puberty in boys.3,4
8 {+ E! G$ F4 }5 AThe most common form of congenital adrenal
$ j: I% E. R; l( N' P1 k; Chyperplasia is the 21-hydroxylase enzyme deficiency.1 c% E% e: a: n6 Y6 l2 S
The 11-β hydroxylase deficiency may also result in
2 C, C/ Z% o7 nexcessive adrenal androgen production, and rarely,1 `: L9 ~. Y7 @7 H: V- J; ]. ~, W
an adrenal tumor may also cause adrenal androgen
" a3 K) D) `' X2 Qexcess.1,3
" d" q/ E$ b* C( v2 G3 O: y% f4 l- Yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
; _" N2 q/ ~ h$ n) S8 c/ A6 D542 Clinical Pediatrics / Vol. 46, No. 6, July 2007! n e3 j* h- B9 ?% h' o3 i
A unique entity of male-limited gonadotropin-& I( W0 b4 {% _, I8 P* q; a
independent precocious puberty, which is also known
& G/ t% J- |) i" N2 R N. n; Las testotoxicosis, may cause precocious puberty at a
) E( P: G- E, o2 b, Gvery young age. The physical findings in these boys
( _5 F+ p. j4 K% n" C- swith this disorder are full pubertal development,; O9 c0 e3 H7 B4 F8 E- L) U
including bilateral testicular growth, similar to boys/ L5 v$ _$ ?7 y$ s! X/ k. y
with CPP. The gonadotropin levels in this disorder m* b% x9 i6 I: q) x; Z
are suppressed to prepubertal levels and do not show9 t5 R/ Z6 J+ s4 p& s
pubertal response of gonadotropin after gonadotropin- I/ W" F- B% S8 A7 V. _
releasing hormone stimulation. This is a sex-linked. s: e$ A, M1 I \% a' z
autosomal dominant disorder that affects only& s0 |/ x( z; `8 b& @
males; therefore, other male members of the family
6 q* \0 x% W( F8 pmay have similar precocious puberty.3
" |- T8 @9 x' W3 s0 {; [% B0 k* mIn our patient, physical examination was incon-
0 X( i4 u' E$ {; c" X9 Tsistent with true precocious puberty since his testi-, U6 U6 P% g4 o2 q% u: o
cles were prepubertal in size. However, testotoxicosis0 C6 H* y# b$ _5 \; e) d* e: X3 F
was in the differential diagnosis because his father
4 a y0 w* A3 W- \' v3 Ostarted puberty somewhat early, and occasionally,2 J+ k7 Y9 f/ i$ y) ?% ^ g; s G
testicular enlargement is not that evident in the; Z9 L/ u& P6 H$ I
beginning of this process.1 In the absence of a neg-! x7 ]& j: b, r
ative initial history of androgen exposure, our0 v/ Y' g# m7 M L2 ^
biggest concern was virilizing adrenal hyperplasia,$ P7 o8 p# x5 {
either 21-hydroxylase deficiency or 11-β hydroxylase- V7 Y- Q/ K6 J+ g; B- x
deficiency. Those diagnoses were excluded by find-
* d) S- }4 Q4 V8 i2 W2 r& Ming the normal level of adrenal steroids.( i$ @0 t# _# k
The diagnosis of exogenous androgens was strongly, N# s2 |9 C1 Y8 g& e
suspected in a follow-up visit after 4 months because
1 _7 v1 f" ^9 x( a, a' L( Z; ^the physical examination revealed the complete disap-0 R. @4 {' i% c, S
pearance of pubic hair, normal growth velocity, and
# z! _! i V; I, l& D. b7 ldecreased erections. The father admitted using a testos-% R: K" {1 }0 R& b0 v/ a$ z
terone gel, which he concealed at first visit. He was
3 v8 M" K( K: busing it rather frequently, twice a day. The Physicians’& Z3 f; w5 E0 B
Desk Reference, or package insert of this product, gel or9 P0 Y+ Q# J7 E) I- B$ ]# W
cream, cautions about dermal testosterone transfer to* w6 \, _4 j- K& T; t1 `
unprotected females through direct skin exposure.' N! a: L, ^/ E. p5 j; Y
Serum testosterone level was found to be 2 times the
# Y+ n" g% X- Q7 vbaseline value in those females who were exposed to d! I% @' T5 q6 |1 m% E6 x
even 15 minutes of direct skin contact with their male& Z/ v- U1 Z/ ], W4 e
partners.6 However, when a shirt covered the applica-3 k- }6 @! g; H
tion site, this testosterone transfer was prevented.
2 E8 g7 p3 x# LOur patient’s testosterone level was 60 ng/mL,
' D/ T0 K# z/ a1 Z$ qwhich was clearly high. Some studies suggest that7 s% h" g) Q' E E$ }
dermal conversion of testosterone to dihydrotestos-
& ~$ o' G) d5 D$ mterone, which is a more potent metabolite, is more6 @: l! M$ z% `
active in young children exposed to testosterone
# M$ D- _5 r. d& k9 H# V, ^exogenously7; however, we did not measure a dihy-
& v) B) t: w/ \7 K! ?drotestosterone level in our patient. In addition to
0 p% S1 A, N6 ]; e' x' vvirilization, exposure to exogenous testosterone in
, R) ~0 U7 R3 H' \ q: g; G! Cchildren results in an increase in growth velocity and: E% z. ~' H1 U) X/ g
advanced bone age, as seen in our patient.
7 x) U9 A( l B0 c1 eThe long-term effect of androgen exposure during
; ?% p9 N" g! p7 n6 bearly childhood on pubertal development and final- u8 ~# A, L3 W1 _
adult height are not fully known and always remain
$ W2 s' V8 s# K( ]3 qa concern. Children treated with short-term testos-
/ P n3 u& Z; Z% H& K3 i7 ]terone injection or topical androgen may exhibit some
% e& b- |: K+ O6 _; Q& T" }acceleration of the skeletal maturation; however, after0 z$ r7 K4 ]* g5 i2 r
cessation of treatment, the rate of bone maturation5 c2 Y# u' O. n+ l* i; U/ Y) W/ ^
decelerates and gradually returns to normal.8,9/ {7 y# n9 s+ a( P+ r/ G
There are conflicting reports and controversy
* X( |) r0 o# \1 c, Hover the effect of early androgen exposure on adult
( q" M+ E8 g4 ?5 q/ {penile length.10,11 Some reports suggest subnormal1 O4 ]) A6 J& \/ @- C
adult penile length, apparently because of downreg-
" t3 |+ w* }5 e" [3 X8 K% m- {6 ?ulation of androgen receptor number.10,12 However,
9 O6 c# `8 r: xSutherland et al13 did not find a correlation between
: T$ V' R- y) y4 E) N& @+ v; @" Lchildhood testosterone exposure and reduced adult& g. a- d' e/ Q! @! O3 s
penile length in clinical studies.) |9 c! P! G* }8 m) d0 r; c
Nonetheless, we do not believe our patient is
" p9 O) C0 c8 ~( a4 Jgoing to experience any of the untoward effects from
- k( @! N0 r7 \9 t' s; Etestosterone exposure as mentioned earlier because
; i4 Q' f2 Z, Mthe exposure was not for a prolonged period of time.# Q5 _: {* e" V$ `/ O5 u! }# i: S4 g
Although the bone age was advanced at the time of
8 p- V' [; n$ `7 `" p4 Adiagnosis, the child had a normal growth velocity at
, F0 G1 j2 [8 e/ L; dthe follow-up visit. It is hoped that his final adult E: e V$ u9 _1 \! F5 Q0 R
height will not be affected.* j. n! p! W4 x. |$ q2 y
Although rarely reported, the widespread avail-
$ ]2 U M/ X$ b$ ]1 {7 gability of androgen products in our society may$ K7 O" N/ D' C
indeed cause more virilization in male or female* ^/ E% D( z. [ o+ j! q( D
children than one would realize. Exposure to andro-
/ Q9 l/ s7 [0 D" n/ [. t& n6 Ngen products must be considered and specific ques-
2 r3 h+ z- ~, @tioning about the use of a testosterone product or
- z/ Q/ X" g. a+ i6 w% d' v- cgel should be asked of the family members during" i# M6 L5 b4 \, \1 P' Y
the evaluation of any children who present with vir-% |# l( ~ n- q% h* f
ilization or peripheral precocious puberty. The diag-! w& Q( |6 R! d8 l& ~
nosis can be established by just a few tests and by
6 Y# }+ b$ J/ R' L2 e+ Q4 S! | Rappropriate history. The inability to obtain such a; \. W/ t# m2 Q
history, or failure to ask the specific questions, may
6 w5 T& Y5 l' i" Jresult in extensive, unnecessary, and expensive) |+ O3 a( y/ N4 m. D; ?8 u H
investigation. The primary care physician should be2 c" U( U$ A' j; J6 F& Y
aware of this fact, because most of these children
) p9 Z; Z9 ~& B. [3 G9 Tmay initially present in their practice. The Physicians’" c! s0 r: O/ r% S8 L; l
Desk Reference and package insert should also put a: f( s8 K* F V. c7 n- z& s
warning about the virilizing effect on a male or
5 T/ E2 w K+ V3 \ Q" x) v0 qfemale child who might come in contact with some-
/ ~1 I6 `8 G2 `5 Q( u5 v2 z1 N. sone using any of these products.5 J: R, T3 U) f5 Z, E: L- v+ v* q
References
+ V+ ]1 v! ^: }- s9 \1. Styne DM. The testes: disorder of sexual differentiation
7 Z) _/ i; M1 f, Land puberty in the male. In: Sperling MA, ed. Pediatric! J5 d5 \' M/ ]
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;3 t# m2 u% N8 H0 p! V# i* ?
2002: 565-628.9 `, O' E, f, W# X
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious! s4 L9 {( v2 ~" L* S
puberty in children with tumours of the suprasellar pineal |
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