- 註冊時間
- 2023-5-6
- 精華
- 在線時間
- 小時
- 米币
-
- 最後登錄
- 1970-1-1
|
發表於 2025-1-4 03:27:02
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old$ H/ c/ _% N$ J. I. \
Boy Induced by Indirect Topical7 L0 e% l2 f3 ~- Y& M: G
Exposure to Testosterone
l* M/ b a2 {" F* uSamar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,21 Z7 t8 R, z8 w5 S: { ]
and Kenneth R. Rettig, MD1
) c6 I1 V2 t# R* L! nClinical Pediatrics& w8 B, L* k$ o6 y5 y6 P5 j
Volume 46 Number 6
+ x+ G& K' \7 HJuly 2007 540-543( C# n; Y# o$ J' A) ^7 ], G
© 2007 Sage Publications
* x8 H/ w! _3 \; b2 D10.1177/0009922806296651- O& v5 H9 b( g4 C8 y) p( f
http://clp.sagepub.com8 }4 m+ |" v' f4 j* M
hosted at4 T- i8 I% H) K& J
http://online.sagepub.com
, k! m# r$ q2 t% N% kPrecocious puberty in boys, central or peripheral,) Q( F' N* j, t( c& i# G1 J* P
is a significant concern for physicians. Central# ?! B5 A# F2 L# [3 ~9 x' Z- h
precocious puberty (CPP), which is mediated
' r* r4 D- [4 M; g; v# }through the hypothalamic pituitary gonadal axis, has; o) h' \& e- J& @
a higher incidence of organic central nervous system
% P3 q# K( O' K: _) s3 Z0 klesions in boys.1,2 Virilization in boys, as manifested
/ A5 j5 v1 b! W5 b4 [8 x. ^by enlargement of the penis, development of pubic8 s2 q$ ~/ G6 I: O# ~) ]
hair, and facial acne without enlargement of testi-
3 Y$ k8 _& B8 y/ p1 Jcles, suggests peripheral or pseudopuberty.1-3 We0 Z6 V5 v% C5 q& S7 v) c0 r
report a 16-month-old boy who presented with the
4 r* M* [/ a* [ p4 Fenlargement of the phallus and pubic hair develop-% v6 g' w: n0 m4 T$ @
ment without testicular enlargement, which was due
. i) k; _: o) `; a( l! r8 Kto the unintentional exposure to androgen gel used by+ I/ @2 ?2 K5 T
the father. The family initially concealed this infor-
( m* _& |! H2 h# ], j* S! Fmation, resulting in an extensive work-up for this/ o4 \8 e) x- `
child. Given the widespread and easy availability of4 R1 }0 m; O: o8 m
testosterone gel and cream, we believe this is proba-+ X. M5 I. k% c4 ~, h
bly more common than the rare case report in the1 @" Y% t8 u0 O- j1 S6 k x
literature.4' p+ v& F9 z. x# }( C. ?% N" T2 T
Patient Report& h; X4 U' d8 z" z3 ]
A 16-month-old white child was referred to the
: ^6 a) C6 S) }1 H5 Jendocrine clinic by his pediatrician with the concern
' a! y: @3 V+ n; w2 n S/ U/ oof early sexual development. His mother noticed
, s: S$ o0 f8 Z/ d5 ^light colored pubic hair development when he was$ P# w l* X3 g$ l8 A: [# d* v+ o
From the 1Division of Pediatric Endocrinology, 2University of1 w' _+ z! V" K7 v
South Alabama Medical Center, Mobile, Alabama.
) B( Q% z( P7 M, wAddress correspondence to: Samar K. Bhowmick, MD, FACE,- b, z7 S4 T2 j$ Z* H: m {4 m
Professor of Pediatrics, University of South Alabama, College of
; e ^ a$ N0 `2 c; eMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
; k! q" x, N$ J: B$ f: I/ Ie-mail: [email protected].
9 n2 \- {# ]2 j: q+ R$ g3 mabout 6 to 7 months old, which progressively became0 s, S/ d& [) M) I
darker. She was also concerned about the enlarge-
: R; Z7 S2 a8 ^2 Dment of his penis and frequent erections. The child* N% ]3 p* d. t, n, ~: ^
was the product of a full-term normal delivery, with
* y! p: O3 {9 T& e4 D& @2 t: T. la birth weight of 7 lb 14 oz, and birth length of
% ?2 H s' q( ?20 inches. He was breast-fed throughout the first year
5 r6 R- R5 h7 o; A dof life and was still receiving breast milk along with% G' D# P' L( w
solid food. He had no hospitalizations or surgery,$ X7 S$ V6 z5 M4 |$ F7 N& X
and his psychosocial and psychomotor development
2 B7 U; w5 X$ W5 f! Zwas age appropriate.
# j7 R0 t. S! t5 ^9 G; H' mThe family history was remarkable for the father,2 O. {; r- K+ Y
who was diagnosed with hypothyroidism at age 16,
! z* {. f3 g7 W/ b8 t1 fwhich was treated with thyroxine. The father’s! Y4 j% A5 c& g( i5 O+ \4 V8 n
height was 6 feet, and he went through a somewhat
! ? U6 @1 P8 A4 Y N mearly puberty and had stopped growing by age 14.
; }4 u. @3 i8 iThe father denied taking any other medication. The9 L9 P* w# o4 t3 _
child’s mother was in good health. Her menarche" J7 n0 I& o2 m: P! F
was at 11 years of age, and her height was at 5 feet
1 m) b: {& l" N6 b% C0 D; X6 F5 inches. There was no other family history of pre-
$ w4 W7 ^7 g8 ^' {cocious sexual development in the first-degree rela-
9 R- n" i' j8 m$ f2 Q, Mtives. There were no siblings.
" x7 I! ^) x, y; l! vPhysical Examination
+ o+ i& |" x" C+ K8 R1 C8 jThe physical examination revealed a very active,) o" m4 }3 d1 \3 ?" t. K9 E& I5 t6 l
playful, and healthy boy. The vital signs documented5 _! |6 f2 c, a7 T# A+ _% x4 F+ r- p
a blood pressure of 85/50 mm Hg, his length was4 [: k& z" L+ u: H* n I
90 cm (>97th percentile), and his weight was 14.4 kg, e* S" P0 h" G% J$ t8 }* T- R
(also >97th percentile). The observed yearly growth
' u+ Q) G+ h2 c! @velocity was 30 cm (12 inches). The examination of
* I% ? b% C! b) o5 cthe neck revealed no thyroid enlargement.
, g3 `: [2 p- V% I. c2 J' |/ |The genitourinary examination was remarkable for
* @# ^3 M% v$ k, K9 wenlargement of the penis, with a stretched length of! X4 n, r7 j/ x" X
8 cm and a width of 2 cm. The glans penis was very well
3 c6 d' b H& e. P1 B+ f8 s. C3 h; gdeveloped. The pubic hair was Tanner II, mostly around0 x1 H+ b# ]/ i; E* y2 D
540- s3 h" \! @2 B5 v; g1 Y3 o
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
3 y/ s$ I) w) a0 j# R+ bthe base of the phallus and was dark and curled. The
w( A2 |0 X9 J) | r( itesticular volume was prepubertal at 2 mL each.0 P6 G6 Q. _- Z2 ^1 Q
The skin was moist and smooth and somewhat
; T- _4 [; j) \6 Moily. No axillary hair was noted. There were no
9 A: h- m( N, n9 O5 J0 |abnormal skin pigmentations or café-au-lait spots.
9 v" z9 Z& C: j, ]1 E% BNeurologic evaluation showed deep tendon reflex 2+. D! W }7 j) |1 y) M4 [3 @) i
bilateral and symmetrical. There was no suggestion
0 X" j) g; |% m- j0 Iof papilledema. U. V7 Z5 B2 V* Q0 T/ a8 h9 a
Laboratory Evaluation
* p* \6 p$ O$ N% } k6 F9 BThe bone age was consistent with 28 months by
. U! I v& Y$ Q5 Cusing the standard of Greulich and Pyle at a chrono-, E% A# C+ p; w. A6 C! b1 X
logic age of 16 months (advanced).5 Chromosomal
" i7 l7 H( N& Qkaryotype was 46XY. The thyroid function test( b2 z8 Q7 q2 T# D8 N; j/ \8 A' T
showed a free T4 of 1.69 ng/dL, and thyroid stimu-, h6 ~" c# }0 X1 O# ^
lating hormone level was 1.3 µIU/mL (both normal).- @6 Q# @* P( o% G
The concentrations of serum electrolytes, blood& k7 A& T3 s3 `1 E: K1 O
urea nitrogen, creatinine, and calcium all were2 D: U% O0 {0 C' x% _" B
within normal range for his age. The concentration
, {( g+ u* a- u/ s5 g& A, [9 Sof serum 17-hydroxyprogesterone was 16 ng/dL
7 W& m; G7 q' Y7 B& i$ k(normal, 3 to 90 ng/dL), androstenedione was 206 q; Y. A9 H& E2 f, e
ng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-' n8 M' E6 {5 X2 g" R/ \
terone was 38 ng/dL (normal, 50 to 760 ng/dL),3 ^% H: A1 S) G; k9 o" S
desoxycorticosterone was 4.3 ng/dL (normal, 7 to Z/ X- }! R1 y ?1 j3 I
49ng/dL), 11-desoxycortisol (specific compound S)
& l, R9 M" y3 a3 ~4 ~was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-
! v" ?: H0 }3 d* n9 e0 A- Stisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total
& m4 s; ^ U' a- f7 J" U8 S. }6 N7 h' Itestosterone was 60 ng/dL (normal <3 to 10 ng/dL),
( q; x9 c$ V* S" b# ^and β-human chorionic gonadotropin was less than: D5 F0 y+ ^% Z5 d
5 mIU/mL (normal <5 mIU/mL). Serum follicular
2 ~* p& m; o! J0 istimulating hormone and leuteinizing hormone$ J/ c$ [7 ^. \# f2 R# C
concentrations were less than 0.05 mIU/mL" J$ ?2 k5 x, w
(prepubertal)., c* G8 F- v/ v8 `
The parents were notified about the laboratory9 h2 ~! q' H# M( t' n8 |, [
results and were informed that all of the tests were. G- j; \" H+ G1 ?+ \* @, c( Y
normal except the testosterone level was high. The
% o6 Z2 S5 P, s- Hfollow-up visit was arranged within a few weeks to
4 I9 u) }+ L7 r- @% kobtain testicular and abdominal sonograms; how-5 {! L9 i9 S2 K
ever, the family did not return for 4 months./ y2 A# B, y- F, G( o9 E
Physical examination at this time revealed that the" c& ]2 W* W0 m; B6 d2 n9 V- t' {7 e
child had grown 2.5 cm in 4 months and had gained2 t2 b" U8 C5 i9 m& j
2 kg of weight. Physical examination remained! E; X; c/ J" S- _0 V
unchanged. Surprisingly, the pubic hair almost com-
4 M7 k3 B, D8 J' E: `+ Vpletely disappeared except for a few vellous hairs at4 v: I: x7 d J. r+ y5 X. L
the base of the phallus. Testicular volume was still 2
- s$ C0 C/ N' E- t1 c( RmL, and the size of the penis remained unchanged." ?/ z. R; r2 g1 H
The mother also said that the boy was no longer hav-
1 d: K2 B: }* A, B/ X5 ying frequent erections.
' n7 j4 L* L! l: P M- Q. t& HBoth parents were again questioned about use of0 x5 d8 q# _5 c) X* a! l7 x
any ointment/creams that they may have applied to5 f% h4 `4 {& y+ h
the child’s skin. This time the father admitted the# ]9 [. X+ L8 j
Topical Testosterone Exposure / Bhowmick et al 541
' h. ?" P; T4 h3 puse of testosterone gel twice daily that he was apply-5 V* v. d: h9 ^3 H& f( |
ing over his own shoulders, chest, and back area for: ~- P$ @% m4 q E4 ]1 W, E
a year. The father also revealed he was embarrassed, g$ w1 F8 A+ Y6 C# k
to disclose that he was using a testosterone gel pre-% g2 f7 H/ `+ B5 c! {
scribed by his family physician for decreased libido
4 D9 E( B" [' g# K5 R) X. j: R& s0 vsecondary to depression.
( [' g3 D5 a6 \( wThe child slept in the same bed with parents.
# f% I3 `5 t( U1 F( `) tThe father would hug the baby and hold him on his
, s2 r- B8 h$ |5 S1 u) y6 C9 tchest for a considerable period of time, causing sig-( H `% g, p4 x4 v
nificant bare skin contact between baby and father.
' W8 D2 a/ e6 }# G% T; rThe father also admitted that after the phone call,; ^4 X9 B, f# C. Z9 Q
when he learned the testosterone level in the baby
4 [8 L* r* s6 O5 P! u, b/ wwas high, he then read the product information
8 G3 D: d2 s; Bpacket and concluded that it was most likely the rea-1 w1 T' n$ h" z
son for the child’s virilization. At that time, they- Q2 k: ^. d* d
decided to put the baby in a separate bed, and the/ z: ? D% q% q6 X
father was not hugging him with bare skin and had* E1 _( I% }$ R1 {* R ?
been using protective clothing. A repeat testosterone
$ T- A, A O' ]& k etest was ordered, but the family did not go to the
+ N, V, [! d. m' zlaboratory to obtain the test.
/ L$ K5 n7 @0 z& Y4 iDiscussion- y' [# n% R7 ?7 e6 B, L
Precocious puberty in boys is defined as secondary% v" l8 G/ g# L
sexual development before 9 years of age.1,4; b. z# C ]! x1 b
Precocious puberty is termed as central (true) when' f @; `: J3 @$ s/ X9 X
it is caused by the premature activation of hypo-# K7 j2 D2 R' g) i) u
thalamic pituitary gonadal axis. CPP is more com-. }, ?8 t3 T }& `7 S% e
mon in girls than in boys.1,3 Most boys with CPP, x: I3 `" b' V8 |1 n
may have a central nervous system lesion that is1 K$ E m7 j; h+ b- E
responsible for the early activation of the hypothal-
8 K3 x1 H2 o( t- bamic pituitary gonadal axis.1-3 Thus, greater empha-
. P0 ~$ @# n4 Q$ ` Lsis has been given to neuroradiologic imaging in
- o( [. p9 i; ~! gboys with precocious puberty. In addition to viril-. s" [# V7 L4 [' ~" L
ization, the clinical hallmark of CPP is the symmet-
6 ?9 g$ V, V: {& e, R- y$ prical testicular growth secondary to stimulation by
" T7 P- B' j0 U* Z) V; a" v: ]gonadotropins.1,3( C* P; f, O- \7 r& W
Gonadotropin-independent peripheral preco-
3 v/ z, Y, Z- w ?7 b" r1 A" ecious puberty in boys also results from inappropriate( e0 H7 c/ s9 `3 \
androgenic stimulation from either endogenous or
- B% F$ h( F- qexogenous sources, nonpituitary gonadotropin stim-
1 A, L. ^) a( ?) _& ~6 Wulation, and rare activating mutations.3 Virilizing
" S% u" S' D5 H% U% h8 c7 Zcongenital adrenal hyperplasia producing excessive* @2 e( u' i& U$ e, P B- q
adrenal androgens is a common cause of precocious# K; C1 T7 n* I1 d4 v
puberty in boys.3,4
% X- p, y/ a! G. j, OThe most common form of congenital adrenal* x" }$ a4 m2 @! d I
hyperplasia is the 21-hydroxylase enzyme deficiency.9 M% ~. U& w5 S" n4 J; \; W
The 11-β hydroxylase deficiency may also result in! ^) l3 W8 o5 r! O9 z8 G$ k
excessive adrenal androgen production, and rarely,
3 h# @4 O6 x4 P0 i+ s* a: v& t ban adrenal tumor may also cause adrenal androgen1 ?5 A. h/ G2 I! n7 P
excess.1,3' X6 F& A4 h6 b3 ]
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from8 D j7 r% W+ D! Z
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
2 |& a. B. p6 h. m6 k% HA unique entity of male-limited gonadotropin-2 ]- @( G8 O9 g0 p3 l
independent precocious puberty, which is also known" V, v$ ]. c2 j% _4 Y
as testotoxicosis, may cause precocious puberty at a4 f4 M3 O' _7 H" l+ _2 O% z9 { ^2 N+ S
very young age. The physical findings in these boys
* _& z" S; `1 V' [4 L3 j5 m7 uwith this disorder are full pubertal development,
( ~6 B5 S& U0 J# l9 Q2 }9 d" oincluding bilateral testicular growth, similar to boys
; e% P& E: B" [7 k- w: @' k* owith CPP. The gonadotropin levels in this disorder
2 T _. I3 G& b5 O3 bare suppressed to prepubertal levels and do not show& Y, M, F0 f* w
pubertal response of gonadotropin after gonadotropin-
9 \0 k8 X& H& nreleasing hormone stimulation. This is a sex-linked( _2 m1 F$ L" N/ q
autosomal dominant disorder that affects only
6 j1 D4 D% T2 _2 u- [males; therefore, other male members of the family( \5 _6 V7 D! @- m$ x
may have similar precocious puberty.3
e: ]4 U8 O4 G0 e& p1 [ R8 G; GIn our patient, physical examination was incon-
6 P+ [3 w, l/ t% Isistent with true precocious puberty since his testi-8 }$ R; v3 ? _" T
cles were prepubertal in size. However, testotoxicosis R: W1 Q j+ m$ X7 u* J
was in the differential diagnosis because his father
; _# ]0 u- ?% nstarted puberty somewhat early, and occasionally,. u3 i, \" s. h5 }
testicular enlargement is not that evident in the
/ [' j* l8 G1 ~: P- ^beginning of this process.1 In the absence of a neg-2 }, y4 A: M8 d) B
ative initial history of androgen exposure, our0 T% ?+ B0 ?3 _7 N+ l! m
biggest concern was virilizing adrenal hyperplasia,4 Y! S% @7 l" W5 K v- |
either 21-hydroxylase deficiency or 11-β hydroxylase
7 _& x: ]' [6 y2 u/ N2 [! o; v" Udeficiency. Those diagnoses were excluded by find-
( n4 J% Y3 F5 Z* }; }3 D/ |ing the normal level of adrenal steroids.
8 T% N) H9 P) i, K! j3 XThe diagnosis of exogenous androgens was strongly' M& A3 r9 x! N' y- x' x3 x
suspected in a follow-up visit after 4 months because- L8 H# X# G2 |& |
the physical examination revealed the complete disap-2 j: v' }# [/ c
pearance of pubic hair, normal growth velocity, and
5 m& k% |! j. a9 ?! E% ]decreased erections. The father admitted using a testos-( w6 R$ u2 i# @
terone gel, which he concealed at first visit. He was: ?2 R% v, ` E3 t- B Y
using it rather frequently, twice a day. The Physicians’
0 ^- W6 W4 Y; g6 n9 fDesk Reference, or package insert of this product, gel or ?( X; J E. X2 O1 d& h
cream, cautions about dermal testosterone transfer to2 m [ p, Z$ x
unprotected females through direct skin exposure.
, P( `# y6 h1 J1 P4 r: @Serum testosterone level was found to be 2 times the0 l" i {+ a' b) F: f
baseline value in those females who were exposed to4 j& @2 d$ J* m2 C% Y
even 15 minutes of direct skin contact with their male
8 _* P: @! z, [% A) t) hpartners.6 However, when a shirt covered the applica-
3 q4 J- Q7 f6 N* D: Etion site, this testosterone transfer was prevented.
( I+ ?, m! I% G/ ^& I& nOur patient’s testosterone level was 60 ng/mL,
# p5 p1 K; S/ U' Pwhich was clearly high. Some studies suggest that
6 @0 `( l2 L% i+ }- d7 Kdermal conversion of testosterone to dihydrotestos-
% R* i% |3 q* z. x, v7 @1 \; H3 x4 Sterone, which is a more potent metabolite, is more( D$ F7 y5 L. ~6 w. g, I
active in young children exposed to testosterone" o; Y, s7 J# w/ U
exogenously7; however, we did not measure a dihy-* G4 S9 K- {0 h% |0 D
drotestosterone level in our patient. In addition to1 L6 A& u% Q% o9 |- a
virilization, exposure to exogenous testosterone in2 p% z; [$ z' o$ x! \) B. s, k8 a
children results in an increase in growth velocity and! i6 n; j8 f9 B- q; V6 D( a) X6 t
advanced bone age, as seen in our patient.
/ P6 U+ \& a2 _9 U6 ]/ fThe long-term effect of androgen exposure during! p3 |3 J+ ]! U( U. W. ~% P
early childhood on pubertal development and final0 t/ D* A: U- g7 {1 R2 G
adult height are not fully known and always remain
$ n" I% Z( A9 P+ Aa concern. Children treated with short-term testos-
2 k2 k5 |+ E! W: p" ?: Z3 tterone injection or topical androgen may exhibit some
* P; ?6 R( r+ Xacceleration of the skeletal maturation; however, after& f5 q5 C+ f3 M" S1 L
cessation of treatment, the rate of bone maturation8 L z& h# ?- t
decelerates and gradually returns to normal.8,9) c7 C8 Y- d# W0 R& z4 r/ f# s
There are conflicting reports and controversy9 A4 G' a! `6 Q1 n
over the effect of early androgen exposure on adult4 p+ ~ F7 ]2 Y: l) u
penile length.10,11 Some reports suggest subnormal
( r7 X1 ?" j8 \. \adult penile length, apparently because of downreg-
3 b4 B1 s, m" k2 o- lulation of androgen receptor number.10,12 However,
: D, @, s: m; p: X+ tSutherland et al13 did not find a correlation between& E% u# P, \. A1 b, a$ q- ~4 F: a+ b
childhood testosterone exposure and reduced adult
1 v0 H/ I' p& v1 I$ \' tpenile length in clinical studies. |/ P3 X H8 `; k f
Nonetheless, we do not believe our patient is& n: b7 x1 f- j. T( e% J; l: a4 b8 k/ t
going to experience any of the untoward effects from
/ E- J1 D; @0 V5 ttestosterone exposure as mentioned earlier because3 E8 B) j, p' A9 t$ j
the exposure was not for a prolonged period of time.3 K$ K! e3 N; x0 x
Although the bone age was advanced at the time of
; R# m6 v8 Q; F% a) K& l9 gdiagnosis, the child had a normal growth velocity at/ [2 m) a3 U8 q
the follow-up visit. It is hoped that his final adult. q5 Q! B; j" q0 L$ G% {
height will not be affected.
$ d8 K. E* T" n+ \7 B0 v- LAlthough rarely reported, the widespread avail-) m8 j2 x: K" @% z- y0 x% `# J" t# }: c
ability of androgen products in our society may- Q1 i& K- ]. j! v* a1 s: d! I
indeed cause more virilization in male or female
% m5 P* ~$ `+ q3 k& Kchildren than one would realize. Exposure to andro-6 E3 ]- \3 p6 K, {5 Y5 E2 c3 ~ @
gen products must be considered and specific ques-
, @: o/ x+ a7 B8 m( p2 mtioning about the use of a testosterone product or0 R* J3 N; s) }0 g3 q
gel should be asked of the family members during
1 V- m' Q9 U. T- P) Mthe evaluation of any children who present with vir-& R2 M3 w- C6 W8 Y- G( c. H7 ]
ilization or peripheral precocious puberty. The diag-) p8 I; j. G* q$ r' y+ D3 T1 A
nosis can be established by just a few tests and by6 g. A3 I6 } f6 E- u3 X
appropriate history. The inability to obtain such a
+ |, U( z$ Y% v( G! Y9 @2 l' d* V1 _history, or failure to ask the specific questions, may3 h, v7 a: p/ Z" ^
result in extensive, unnecessary, and expensive
8 ^( z0 Z" Z% c: ~# z! S4 Kinvestigation. The primary care physician should be
4 d v" K: P( ~2 P# waware of this fact, because most of these children
0 O6 o& f7 c. f! n% `* Dmay initially present in their practice. The Physicians’: b: l+ W6 _+ t; m2 [ p! R- i, z
Desk Reference and package insert should also put a
6 q5 `& J5 w) |* D6 w: O- Cwarning about the virilizing effect on a male or8 x% l, Q* i& A
female child who might come in contact with some-
4 t+ g1 [# w# R; ~5 H0 ^0 Sone using any of these products.9 I8 W p6 u9 r k# J/ I
References
) M+ s5 Z9 O) N6 A2 O# V" M1. Styne DM. The testes: disorder of sexual differentiation) P/ B/ E6 l s' R. [+ @1 _
and puberty in the male. In: Sperling MA, ed. Pediatric
w, K* h( `' OEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;4 H* D1 |$ V3 I4 H5 G; f! J: q
2002: 565-628.
. c" \ M2 I C+ W9 P( y2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious8 n% Z8 r! m7 ~
puberty in children with tumours of the suprasellar pineal |
|