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| Sexual Precocity in a 16-Month-Old 7 R7 W. V- I8 M( D6 ?6 \Boy Induced by Indirect Topical/ A! L5 ?6 r3 x- g' k( d6 A8 f# o
 Exposure to Testosterone1 a" p( ?  \& J$ |- M
 Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
 + z2 U. C2 T- u) R, kand Kenneth R. Rettig, MD1
 5 E4 X5 ^! B! _+ y4 o( YClinical Pediatrics* @0 v0 m2 d3 ^3 Q6 k9 S
 Volume 46 Number 6+ Q; y, `, t: S7 r7 p
 July 2007 540-543" {  N' I9 g% R! h
 © 2007 Sage Publications
 9 c8 i0 Z6 o) A4 D* z" G10.1177/0009922806296651! K' v2 }8 Y, z( G+ I
 http://clp.sagepub.com
 - Q9 H3 Y) Q0 _hosted at
 6 U2 Z' H% b* Khttp://online.sagepub.com
 $ ^+ b  B3 Z& C6 J( S- ]Precocious puberty in boys, central or peripheral,
 2 H" i% k6 A- P( @7 k7 \! qis a significant concern for physicians. Central5 S( O+ Q$ U7 u' p2 b: c! }
 precocious puberty (CPP), which is mediated3 m9 B8 Z- M+ q9 n' l
 through the hypothalamic pituitary gonadal axis, has
 : A: v, ?4 S& R6 L0 ua higher incidence of organic central nervous system
 1 F1 Q9 s+ i9 s% ^lesions in boys.1,2 Virilization in boys, as manifested
 - q3 m/ O& N5 n. o: w( o% ~by enlargement of the penis, development of pubic+ X! S! \0 Q0 G9 G( o
 hair, and facial acne without enlargement of testi-
 / i" Q# d  G2 R1 Gcles, suggests peripheral or pseudopuberty.1-3 We
 ! I$ _  F, i9 |7 \. G6 ureport a 16-month-old boy who presented with the
 $ H! |3 O( o6 e; benlargement of the phallus and pubic hair develop-
 $ f7 {) o$ g& n7 r5 U2 Qment without testicular enlargement, which was due
 $ W6 h" s7 i/ B% ~: ~to the unintentional exposure to androgen gel used by
 . [( @8 |5 `8 L7 _- n& B( zthe father. The family initially concealed this infor-
 , J% \. {2 ~0 i8 t: emation, resulting in an extensive work-up for this' z4 C7 {8 a& G( Q
 child. Given the widespread and easy availability of1 d$ e% G) k1 ]4 i/ [
 testosterone gel and cream, we believe this is proba-: [1 G/ n; k5 }9 l1 b
 bly more common than the rare case report in the5 k5 h6 z8 K0 L& @% O+ u
 literature.43 ^* H( `# v9 e# S1 b7 Z* O
 Patient Report
 : Y( U+ S1 }& z, {! e; {A 16-month-old white child was referred to the4 V. C) _  P  q. S2 j: x9 h
 endocrine clinic by his pediatrician with the concern8 G1 ]& z2 H$ {, Z; G, K* ]
 of early sexual development. His mother noticed
 . s8 [! S5 [4 Tlight colored pubic hair development when he was6 }, n9 a% p/ S5 I# ?+ u/ A) F/ {
 From the 1Division of Pediatric Endocrinology, 2University of. l8 i1 V8 n+ }5 ?' Y! y- e
 South Alabama Medical Center, Mobile, Alabama.
 & L/ Z1 c6 C& I, `8 U' g- l) qAddress correspondence to: Samar K. Bhowmick, MD, FACE,
 2 n- m- z' q5 @" B* ~Professor of Pediatrics, University of South Alabama, College of
 + G1 ]& q* g) M9 N2 N: bMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
 ' C2 c) L8 l% T2 |e-mail: [email protected].- J+ K" h0 _; ?+ `& J0 l; Q9 u5 y
 about 6 to 7 months old, which progressively became7 I; C3 _5 J) w/ l% J- _# r
 darker. She was also concerned about the enlarge-
 2 f, ~5 X) f0 O% D  y8 Zment of his penis and frequent erections. The child$ l$ q: Q' J2 S4 l$ v+ H/ p" a) N
 was the product of a full-term normal delivery, with" c8 n, ?# J( K( S; j
 a birth weight of 7 lb 14 oz, and birth length of9 f$ r8 X3 N# H. U' x* x2 W
 20 inches. He was breast-fed throughout the first year$ |( P) c, B1 f, k1 M7 N4 D
 of life and was still receiving breast milk along with
 , s0 {) b9 x3 n1 a$ T' C! ~0 esolid food. He had no hospitalizations or surgery,7 C; Z  L, V6 ~! R  a5 Q
 and his psychosocial and psychomotor development
 + l: t, T$ p! V* P$ u; J/ `2 }. Iwas age appropriate.6 f: e; ~3 v( J. b
 The family history was remarkable for the father,: t3 v7 o) i' X4 ?
 who was diagnosed with hypothyroidism at age 16,
 % ?' q3 m7 J) t7 L8 u  {6 q  vwhich was treated with thyroxine. The father’s
 # Y/ `! C# E9 ~+ Mheight was 6 feet, and he went through a somewhat. n/ ]: B5 f2 O1 A# T
 early puberty and had stopped growing by age 14.+ @% ], C2 A3 f" P9 j) b9 v
 The father denied taking any other medication. The
 6 s, |9 P2 ~3 m+ rchild’s mother was in good health. Her menarche
 , W/ k& R. a, ~was at 11 years of age, and her height was at 5 feet3 X" {5 j4 U4 z, z
 5 inches. There was no other family history of pre-( i) P1 v7 E, ^9 s1 E, S
 cocious sexual development in the first-degree rela-
 - d" K! u$ y$ H' b0 N; T% E% k3 otives. There were no siblings.
 ' L2 m3 ^* _& v: u. M8 EPhysical Examination
 - S) E5 U3 N) _- y$ zThe physical examination revealed a very active,/ m* W6 r; {7 Y: a
 playful, and healthy boy. The vital signs documented
 ( p, q' K, Z" u- ^4 Fa blood pressure of 85/50 mm Hg, his length was
 $ W; `5 t! s" q- |/ \90 cm (>97th percentile), and his weight was 14.4 kg
 . d/ \4 b: k% _* V, Q: i  B(also >97th percentile). The observed yearly growth
 * o' M, s+ b, Vvelocity was 30 cm (12 inches). The examination of3 @9 T$ l, M2 P" `6 m; c8 A
 the neck revealed no thyroid enlargement.4 z) R# s% ^; Z
 The genitourinary examination was remarkable for& M+ f  o2 o+ X" Z" G3 j0 x
 enlargement of the penis, with a stretched length of, W# c7 x/ j' w- [+ ~
 8 cm and a width of 2 cm. The glans penis was very well
 " s; U! f# [4 F% h# n. `  \developed. The pubic hair was Tanner II, mostly around
 $ y# k6 \$ ~3 C: S1 i+ ]540
 " {/ a1 P+ J; D9 H& i3 rat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
 ! _5 g+ f; y) W3 A+ `) A0 i8 ?the base of the phallus and was dark and curled. The
 ) u9 c4 x; G. p- R* y! ]0 @; ltesticular volume was prepubertal at 2 mL each.! P- R, h: E, D- i6 S; Q; ~9 Y
 The skin was moist and smooth and somewhat
 ( H5 N  V) J4 ~; s9 Y8 \oily. No axillary hair was noted. There were no
 ! Z* R; R' D2 R8 V/ Q/ \5 @abnormal skin pigmentations or café-au-lait spots.( I5 X. |$ G9 ^  {
 Neurologic evaluation showed deep tendon reflex 2+
 4 i2 V4 W! [& v0 m3 h' U+ K& vbilateral and symmetrical. There was no suggestion8 k# z* R* a. ]: P! E% I* q7 f- W
 of papilledema.
 . Z# B5 w0 s' u  R6 W9 }Laboratory Evaluation
 & a- l) ~: d* }& i- Y% {2 n1 WThe bone age was consistent with 28 months by; s4 P1 m1 w, n! H( V- L9 s1 w
 using the standard of Greulich and Pyle at a chrono-
 / c, U* x6 B+ x4 Blogic age of 16 months (advanced).5 Chromosomal& g! w$ H: T( k+ d& d. f" i
 karyotype was 46XY. The thyroid function test2 N& z! u+ B5 p5 Z+ q7 f- D
 showed a free T4 of 1.69 ng/dL, and thyroid stimu-( |; |) g4 d: L- N
 lating hormone level was 1.3 µIU/mL (both normal).
 ' Y, Q$ @" B% A5 k$ I  q5 FThe concentrations of serum electrolytes, blood
 " ]0 U3 X  M) D: @urea nitrogen, creatinine, and calcium all were
 4 F/ k- [; ?6 J! a2 |within normal range for his age. The concentration
 ' |- c" Q: U0 J4 z& R1 z* bof serum 17-hydroxyprogesterone was 16 ng/dL
 : w* S$ J( m4 N" ?. ~(normal, 3 to 90 ng/dL), androstenedione was 200 ^" A- L% E' s% V' B$ q! Z
 ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
 1 s; {) F# a7 L: Bterone was 38 ng/dL (normal, 50 to 760 ng/dL),7 X3 x: p* {8 t: v  ]+ ~8 i4 Q1 n4 E% \
 desoxycorticosterone was 4.3 ng/dL (normal, 7 to
 ; W" o( Z: k# s49ng/dL), 11-desoxycortisol (specific compound S)
 ( t' A- _: i6 h2 [3 Iwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-3 X0 S, `8 ~' W
 tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
 ) ], ]) Y7 n/ c5 c2 m9 M6 jtestosterone was 60 ng/dL (normal <3 to 10 ng/dL),( s% G  S& B! I$ G9 W
 and β-human chorionic gonadotropin was less than7 N& _" V; U' T# c
 5 mIU/mL (normal <5 mIU/mL). Serum follicular
 8 H2 @( d4 E4 P  B& W" `, {9 w3 s- {stimulating hormone and leuteinizing hormone  g0 B% z0 [) S( k7 f! J
 concentrations were less than 0.05 mIU/mL- A4 G! L' h) l7 \# L: ^
 (prepubertal).0 Q, x7 o5 {5 U9 v, X( _1 G
 The parents were notified about the laboratory
 Q$ T6 m/ j, y/ [results and were informed that all of the tests were
 9 A( }1 @- N! A3 L4 c, mnormal except the testosterone level was high. The
 / D1 d0 m& _* x3 D9 ?, bfollow-up visit was arranged within a few weeks to
 5 ?1 F6 A: ]$ x% u; zobtain testicular and abdominal sonograms; how-1 r4 E4 @" w! I2 D% d$ z
 ever, the family did not return for 4 months.) [" _. Y: e- T0 L1 g
 Physical examination at this time revealed that the# J* z* p1 o6 K) [# o2 E" n0 d# f1 R
 child had grown 2.5 cm in 4 months and had gained
 $ X" N( ~. D" k$ G9 t# G) X. A2 kg of weight. Physical examination remained
 " e/ o6 l! u0 M; n1 kunchanged. Surprisingly, the pubic hair almost com-6 P/ f- l. n. B7 O+ X
 pletely disappeared except for a few vellous hairs at
 ( c: f/ i/ Y# y! l. j. f( x8 p4 othe base of the phallus. Testicular volume was still 2  L) G: ?$ N6 e/ \/ ]' _5 p; J
 mL, and the size of the penis remained unchanged.
 ) H' m6 G9 s! N) \3 M7 LThe mother also said that the boy was no longer hav-$ ^' h: S( v; U, C
 ing frequent erections.
 8 A* |# A# }  k' H( eBoth parents were again questioned about use of
 ( G8 c' N1 h! b; `, Xany ointment/creams that they may have applied to
 ) O* \$ C: V1 S% b. z5 n( ?9 Cthe child’s skin. This time the father admitted the; j# d2 ?& f7 F
 Topical Testosterone Exposure / Bhowmick et al 541% ~$ U/ o3 [4 d6 m4 u& a  \( X
 use of testosterone gel twice daily that he was apply-
 ! S# g2 I8 s" d9 P: bing over his own shoulders, chest, and back area for
 6 u9 i8 n# K! ga year. The father also revealed he was embarrassed
 # f2 f; m; f/ J! L4 d1 Uto disclose that he was using a testosterone gel pre-! v; u2 |! V. E5 Q; x; v- L; E
 scribed by his family physician for decreased libido* X) f+ K$ o1 w$ O2 r
 secondary to depression.
 0 F% w  v/ F, r; z: dThe child slept in the same bed with parents.
 $ h3 ?9 i) D9 @) f* q% iThe father would hug the baby and hold him on his6 |2 C/ j. E) U  j! T* D) V4 G
 chest for a considerable period of time, causing sig-+ u( C3 J9 d0 f6 C, e) j
 nificant bare skin contact between baby and father.0 Z2 J% z1 q" R3 C' h' a, c3 x! N
 The father also admitted that after the phone call,. [( |9 Y8 r  C" \
 when he learned the testosterone level in the baby
 5 V1 ^6 ?" C1 j4 Z# ewas high, he then read the product information
 u" Y4 i; z4 l# Dpacket and concluded that it was most likely the rea-
 ) L* t) z$ j6 v. x7 o0 {% Dson for the child’s virilization. At that time, they
 / Y, X9 Q% j' j1 n7 e! F* [9 \decided to put the baby in a separate bed, and the/ U4 v# w. \) U: T
 father was not hugging him with bare skin and had
 ; Q/ j; j* t  ]3 [, Y# P" \! abeen using protective clothing. A repeat testosterone2 D: b$ K1 @) Q8 E! G4 t
 test was ordered, but the family did not go to the: {- A& k+ C. H
 laboratory to obtain the test.
 : X) A2 j0 D  S) ODiscussion! t# t, v! h: C
 Precocious puberty in boys is defined as secondary
 7 d/ c3 M: X& ]+ @8 v8 csexual development before 9 years of age.1,4; V: {5 U/ l4 a" W
 Precocious puberty is termed as central (true) when
 . }- S$ }9 q, P7 mit is caused by the premature activation of hypo-
 $ t" S* i% A) e+ V4 Xthalamic pituitary gonadal axis. CPP is more com-/ W( L, K4 `6 \1 U. E' p% H
 mon in girls than in boys.1,3 Most boys with CPP
 : G7 f  j6 n: L6 ?  w2 i2 K4 Zmay have a central nervous system lesion that is# J) [3 S& S. i# Q
 responsible for the early activation of the hypothal-
 5 v, K0 M9 e8 G1 ]amic pituitary gonadal axis.1-3 Thus, greater empha-; I, i0 v! O- d1 b0 ^! Q5 j$ S
 sis has been given to neuroradiologic imaging in
 9 X5 K' W$ q- {2 b& ?: T  gboys with precocious puberty. In addition to viril-
 9 k# z: H! m6 U2 v2 z" vization, the clinical hallmark of CPP is the symmet-
 7 P, `  h! ~, [8 ^: ]0 u8 mrical testicular growth secondary to stimulation by
 1 j% z+ j: N4 c$ N! t3 Mgonadotropins.1,3
 9 u" R7 x7 ^, g2 A) A: L% uGonadotropin-independent peripheral preco-
 + M% @8 `/ {7 u% @% L" o2 ?cious puberty in boys also results from inappropriate
 ' d; g( m* B" ?5 |3 ^. N: aandrogenic stimulation from either endogenous or
 ; S/ K* ^/ l# d7 H3 ?; Mexogenous sources, nonpituitary gonadotropin stim-* [7 K9 a  m, h. y5 R
 ulation, and rare activating mutations.3 Virilizing' r8 f0 u( Q! H# H
 congenital adrenal hyperplasia producing excessive6 x$ R7 ^# U5 k4 J; W; P9 I6 R
 adrenal androgens is a common cause of precocious
 8 f: m' m: E0 ]3 `" qpuberty in boys.3,4
 - ]6 d' o) ~$ E" ZThe most common form of congenital adrenal7 r( k9 j8 d" I. ~! `" I5 t! G
 hyperplasia is the 21-hydroxylase enzyme deficiency.* S5 X5 i" p2 d! _1 }
 The 11-β hydroxylase deficiency may also result in4 {8 A* f( @3 o9 @/ Y
 excessive adrenal androgen production, and rarely,
 5 A. U: I% f, V+ x. B0 a' \9 uan adrenal tumor may also cause adrenal androgen
 1 |) _. A& g1 V: E* R5 Q# ?: Yexcess.1,3
 2 \" T" u* H. i+ P3 L: H/ Q* m' tat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
 5 h9 l) @, h# z! ^* ]0 f- Y' d7 ?542 Clinical Pediatrics / Vol. 46, No. 6, July 2007& F$ X! x( ?  @7 e5 @
 A unique entity of male-limited gonadotropin-: [+ c4 k" w; a. s" L5 `
 independent precocious puberty, which is also known
 6 M- S; l+ D2 |9 [9 j( N/ H6 i4 uas testotoxicosis, may cause precocious puberty at a
 + ^' G1 Z. I6 [: ^very young age. The physical findings in these boys
 . \- y4 P8 h2 Ywith this disorder are full pubertal development,( T3 i& p8 z5 p; J0 [2 ]9 R" i
 including bilateral testicular growth, similar to boys
 , C% |) u( z. u: b8 C& S3 F' r% c8 ywith CPP. The gonadotropin levels in this disorder/ V, X2 s# D! k
 are suppressed to prepubertal levels and do not show
 8 c, r) `; @# hpubertal response of gonadotropin after gonadotropin-
 + e7 @# e) D  `3 }2 v5 K# Sreleasing hormone stimulation. This is a sex-linked5 c' L5 q" J) [: N" w# |: C* ^
 autosomal dominant disorder that affects only; K9 O3 C# }; U! O4 H3 u" V+ q
 males; therefore, other male members of the family
 . B& S- V9 h' zmay have similar precocious puberty.3
 # t- a1 p. b: I# ?+ t* J, N2 AIn our patient, physical examination was incon-
 3 z$ ~% B4 b2 D) ]8 Esistent with true precocious puberty since his testi-0 s3 Q! Y# p# D- D0 B  l
 cles were prepubertal in size. However, testotoxicosis
 & j4 A1 S( }0 H* `( pwas in the differential diagnosis because his father
 + u9 [+ d9 u3 m4 j/ p/ Kstarted puberty somewhat early, and occasionally,
 P+ q  ?- W: A  Y3 ptesticular enlargement is not that evident in the
 $ R+ d. z+ f* I6 A8 P  \( j# fbeginning of this process.1 In the absence of a neg-
 8 [. o% D4 b8 I; f- ~1 T; Aative initial history of androgen exposure, our
 3 I' J& b% @( E; L- x4 ybiggest concern was virilizing adrenal hyperplasia,
 " v+ e" f. Q% _  o, c& I3 yeither 21-hydroxylase deficiency or 11-β hydroxylase
 4 C0 V4 p. a) u. b$ Pdeficiency. Those diagnoses were excluded by find-7 }: P  J! Q$ _7 @. E- C
 ing the normal level of adrenal steroids.$ O9 Y! p& H" c  J% a
 The diagnosis of exogenous androgens was strongly
 0 D1 ~. `- F- U, Ssuspected in a follow-up visit after 4 months because
 ; [8 r' L. P, [# d* U& R4 athe physical examination revealed the complete disap-
 ; M% M- _3 _' o, R2 b+ `. N7 j& opearance of pubic hair, normal growth velocity, and
 f" i, o) {$ e& F- Sdecreased erections. The father admitted using a testos-
 # s7 v1 K0 `4 U+ n/ Lterone gel, which he concealed at first visit. He was
 , q" d! Q% e2 [1 v' k, ^using it rather frequently, twice a day. The Physicians’
 ! U' Q+ B7 v0 M, ~2 U3 V' E/ F& oDesk Reference, or package insert of this product, gel or
 3 c) y' K* y4 u/ i& g  r& W" ^1 Bcream, cautions about dermal testosterone transfer to0 c4 r$ ^* G( V& @+ b$ v! |8 r
 unprotected females through direct skin exposure.
 ) `% c/ C' j$ @/ JSerum testosterone level was found to be 2 times the8 @/ N# j- Z0 f+ e% B( }
 baseline value in those females who were exposed to
 - F9 S9 Q6 n! peven 15 minutes of direct skin contact with their male8 @' X" V0 h* c& J4 @& v: ~
 partners.6 However, when a shirt covered the applica-, |' y& B  @& q" H. O
 tion site, this testosterone transfer was prevented.( l2 U8 R$ m/ B% z7 i) g
 Our patient’s testosterone level was 60 ng/mL,6 G/ W" K& g* ~" `( k
 which was clearly high. Some studies suggest that
 / Z5 D+ ]% a0 [4 h- R2 A& tdermal conversion of testosterone to dihydrotestos-
 0 ]% @" F, X- j: M% S/ L: uterone, which is a more potent metabolite, is more
 4 v' I& K# x! ~% ~1 V) F7 N" ractive in young children exposed to testosterone. U- c( K  a0 C
 exogenously7; however, we did not measure a dihy-4 ?$ e" C3 [( ~8 Q4 F
 drotestosterone level in our patient. In addition to+ v0 E" V2 k, @# X; Q4 W+ G1 T
 virilization, exposure to exogenous testosterone in; S% E: L. B; V  G; }
 children results in an increase in growth velocity and
 - N# O, E" p9 n% zadvanced bone age, as seen in our patient.) W, M% H) G( H; k
 The long-term effect of androgen exposure during0 E! K$ `7 p/ x( c
 early childhood on pubertal development and final" I5 X2 }" s# ]4 {: }% z3 D6 W
 adult height are not fully known and always remain
 ( s" q8 {+ Y! W- t5 a, K( Za concern. Children treated with short-term testos-
 , I1 j3 `. l' V( d! ^2 o3 _4 cterone injection or topical androgen may exhibit some- v, ?% e( @0 h  ~1 k, R5 d
 acceleration of the skeletal maturation; however, after; M. p+ A2 y2 A* d% x
 cessation of treatment, the rate of bone maturation
 2 w- j  A  c6 T& l3 v  ]1 T- u* xdecelerates and gradually returns to normal.8,9
 0 H3 L4 ]" J1 j) _6 eThere are conflicting reports and controversy% q) E6 `0 {. [
 over the effect of early androgen exposure on adult5 p! F1 ]& }, I# R- [
 penile length.10,11 Some reports suggest subnormal
 ( d. w! n0 c6 p: o/ \adult penile length, apparently because of downreg-
 ]7 z( G+ U4 k3 e# m, ~2 X: xulation of androgen receptor number.10,12 However,
 }  r# e4 t+ G7 k: H0 BSutherland et al13 did not find a correlation between' Q0 l" x, x; I3 T% U! Y) o: _
 childhood testosterone exposure and reduced adult" d9 o# M  B& B7 O. d; Y1 I/ A) I
 penile length in clinical studies." E; S2 x1 P0 t& P
 Nonetheless, we do not believe our patient is
 " j- |! b6 Z  r6 wgoing to experience any of the untoward effects from
 % d9 s' |% I$ y: }" w  K- Ntestosterone exposure as mentioned earlier because) k* B* v2 a8 m9 J# H; z& T
 the exposure was not for a prolonged period of time.3 @0 r6 R0 L- o1 Q& o; T
 Although the bone age was advanced at the time of
 # i* r8 M* i! tdiagnosis, the child had a normal growth velocity at$ H& A9 I+ |8 f( g5 e1 V" s
 the follow-up visit. It is hoped that his final adult
 w& O; U+ s. {2 `7 u# L: rheight will not be affected.5 R" a! V5 L  C( E7 y  x: c
 Although rarely reported, the widespread avail-
 % _$ g2 l3 f/ Q& K& lability of androgen products in our society may
 $ A- N% E; @# c( \! Hindeed cause more virilization in male or female, \# o# i$ `" a7 c
 children than one would realize. Exposure to andro-/ I7 O1 H& S- n7 h6 k7 l2 g
 gen products must be considered and specific ques-
 ) U9 B" _4 R7 r9 ltioning about the use of a testosterone product or/ T) Z- T' J) ^
 gel should be asked of the family members during
 5 g: M) E' K2 M1 A* Qthe evaluation of any children who present with vir-0 Y3 ?3 W7 U" T
 ilization or peripheral precocious puberty. The diag-
 9 l6 K7 A) ~- `; A/ Vnosis can be established by just a few tests and by; y$ M# n9 d0 E
 appropriate history. The inability to obtain such a
 6 O8 p0 x% L/ Uhistory, or failure to ask the specific questions, may
 6 K+ t% K8 W2 {; ?& f8 a( o- j2 zresult in extensive, unnecessary, and expensive
 & v8 J) V; Q8 B3 R  C5 `investigation. The primary care physician should be6 m+ G6 y1 r$ {+ M8 ?  w; D, X7 R6 ^" R
 aware of this fact, because most of these children
 % M# Y- b+ ~, u9 E6 bmay initially present in their practice. The Physicians’, B8 ]- P! O5 {5 Y4 E: {
 Desk Reference and package insert should also put a0 E7 S: m, r* h3 N5 y  y
 warning about the virilizing effect on a male or. `# ^" w( u, ~
 female child who might come in contact with some-
 0 _" [/ t# t$ K4 }& d8 Rone using any of these products." w. z$ l0 i# J% E$ P* d
 References
 $ o, D; ?) Y6 n* q1. Styne DM. The testes: disorder of sexual differentiation
 . s  }" _, E; \4 X' c' q8 ^" ?; _1 Mand puberty in the male. In: Sperling MA, ed. Pediatric/ E8 v5 e, Y( s
 Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
 . E9 Z7 J( {4 }, S0 B2002: 565-628.5 B0 l7 n  u/ Q. Y0 _: }7 S& I
 2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious  k+ r1 s& Z* D4 q  n
 puberty in children with tumours of the suprasellar pineal
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