- 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 03:25:35
|
顯示全部樓層
Sexual Precocity in a 16-Month-Old
: ?: M$ j. r9 e4 kBoy Induced by Indirect Topical& m! l! a5 Y" f. u
Exposure to Testosterone4 M) l: _, X9 Y* Y$ g
Samar K. Bhowmick, MD, FACE,1 Tracy Ricke, MD,2
) ?' Z& P) z% V! C- @and Kenneth R. Rettig, MD1 a0 \& l" R" S* |
Clinical Pediatrics
9 u0 a6 G$ w% H! L6 LVolume 46 Number 66 m+ N- D* b$ G* t' Z
July 2007 540-543
9 M( ]( F& T, c# q# s5 I* ~+ ^7 M' x& ]© 2007 Sage Publications
, P: k9 \6 c$ ]8 O10.1177/0009922806296651$ u8 @2 ~# W* j1 b
http://clp.sagepub.com
& U2 d- U2 _ v mhosted at
- ^! z2 |/ F2 P/ Yhttp://online.sagepub.com! e) |: G- F" i j, _5 b
Precocious puberty in boys, central or peripheral,
8 e! ]) K: U1 H4 X8 `is a significant concern for physicians. Central7 z8 f- d$ l2 s
precocious puberty (CPP), which is mediated; f3 n* D# [' S: i0 f
through the hypothalamic pituitary gonadal axis, has
2 _# q9 N" ~; ~0 S1 _a higher incidence of organic central nervous system
4 {5 i) L$ m N% ^* c" I' Elesions in boys.1,2 Virilization in boys, as manifested3 ]" H; @9 k4 E" [+ e% T1 i
by enlargement of the penis, development of pubic, d* u3 [& c3 @/ b
hair, and facial acne without enlargement of testi-
! f$ @; o# r+ Acles, suggests peripheral or pseudopuberty.1-3 We
5 L2 w- y4 S; Q9 T9 zreport a 16-month-old boy who presented with the
, d2 p5 t0 P: Lenlargement of the phallus and pubic hair develop-$ V5 S+ k6 g1 Y3 N
ment without testicular enlargement, which was due: f6 g5 F9 E2 W0 Z& ?, _ p: Y
to the unintentional exposure to androgen gel used by
5 v# @9 A8 L: U Mthe father. The family initially concealed this infor-
, B0 k3 t+ f+ E8 T' gmation, resulting in an extensive work-up for this6 X/ F% ^; @2 K& ]5 I
child. Given the widespread and easy availability of0 I8 w4 U3 i9 j) J& X6 y) L
testosterone gel and cream, we believe this is proba-& s U2 H B& C
bly more common than the rare case report in the* F5 c& D/ C# s! L4 J
literature.4
$ r" p7 a4 H, t! g3 f+ |! g8 @; ?Patient Report
9 R. U) J3 M1 d! s$ \( L) [( l! sA 16-month-old white child was referred to the
' z$ \3 S% G0 pendocrine clinic by his pediatrician with the concern( }+ ~, m+ b# d, ?( z' o# I/ {! g
of early sexual development. His mother noticed
7 y6 m& b2 P) l- I* Tlight colored pubic hair development when he was, n/ Z8 ~" @& f3 }
From the 1Division of Pediatric Endocrinology, 2University of
6 }; v, Y! B1 {& E# {/ _2 K0 PSouth Alabama Medical Center, Mobile, Alabama.. L5 t# V! q' s( w
Address correspondence to: Samar K. Bhowmick, MD, FACE,
8 \- a) f" S, r& @2 S D/ T) ]Professor of Pediatrics, University of South Alabama, College of
" U* F# {6 ^ _8 S' MMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;
7 q0 \* U' j! ?1 C; ]5 Be-mail: [email protected].. |6 b: L& b' I* n. o: g% d+ i2 @
about 6 to 7 months old, which progressively became
, d0 b% _( Q3 ]/ _" x; |' N3 sdarker. She was also concerned about the enlarge-
5 B( n2 M3 F, W9 ^# L9 h0 Sment of his penis and frequent erections. The child* H# C( K/ h8 ]' Z+ H7 z& V) {
was the product of a full-term normal delivery, with2 ]/ u- S) k. ^
a birth weight of 7 lb 14 oz, and birth length of. S0 i3 W9 C* A" Q2 r
20 inches. He was breast-fed throughout the first year3 `+ z8 F- t3 c* s( j" s: @
of life and was still receiving breast milk along with
9 @, M# `) ~9 i- o1 b Ksolid food. He had no hospitalizations or surgery,
+ E7 X% v: W* j$ R. L; a! a* Yand his psychosocial and psychomotor development0 }& V4 F( t6 g1 T
was age appropriate.
; ~) ?: j+ ^1 p: l F% XThe family history was remarkable for the father,
+ |/ }" m+ y+ A: twho was diagnosed with hypothyroidism at age 16,' O4 _8 v$ y9 [* ~
which was treated with thyroxine. The father’s
$ O- u% k' M! C+ i @; m" x! G9 }height was 6 feet, and he went through a somewhat$ V% a0 B6 m9 ?. o% X
early puberty and had stopped growing by age 14.7 B* q& W$ k( k6 Q& m2 R
The father denied taking any other medication. The- S; v( T9 x% G ^. I
child’s mother was in good health. Her menarche
1 p3 u; h) j, twas at 11 years of age, and her height was at 5 feet
/ X3 G. Z3 G5 N! L! `5 inches. There was no other family history of pre-: k; A" C# H- Z# F% w; K$ @
cocious sexual development in the first-degree rela-/ t( n6 R* m- E6 ^5 p- L+ X
tives. There were no siblings.
1 X2 E9 w7 w. J6 u+ jPhysical Examination2 A9 t" L' ]2 m7 a* z7 }& k' z
The physical examination revealed a very active,4 f9 T! }' d. g$ p
playful, and healthy boy. The vital signs documented
5 X5 o1 `# }0 C; ja blood pressure of 85/50 mm Hg, his length was
, v, K5 k, n2 C* f4 ?* h& Y90 cm (>97th percentile), and his weight was 14.4 kg
, s* V, V( y+ P2 F& ^8 z, z(also >97th percentile). The observed yearly growth! d7 M+ j. T, D2 t0 T, n
velocity was 30 cm (12 inches). The examination of& }# T; C9 ^$ d) b; {
the neck revealed no thyroid enlargement.# ~) k1 U& ]! F. F1 J' t3 M
The genitourinary examination was remarkable for
& m) P' y# N6 [0 H: }6 Qenlargement of the penis, with a stretched length of% x- P8 v/ z: l5 M! p$ l, {
8 cm and a width of 2 cm. The glans penis was very well
$ S# z; X! A4 S( u1 ydeveloped. The pubic hair was Tanner II, mostly around: @% J5 V# ?7 [) x
540
% x& x8 x" d4 p1 Y; L2 E; Pat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
7 r% p: g6 n3 Y* f3 \the base of the phallus and was dark and curled. The+ L0 A$ q& r7 m0 V: [8 ? W; W b
testicular volume was prepubertal at 2 mL each.4 M) H, |8 o2 C! v& s" t
The skin was moist and smooth and somewhat
: U8 S) O5 z* v% f8 s* _oily. No axillary hair was noted. There were no
v' R. Z1 a$ |3 labnormal skin pigmentations or café-au-lait spots.
" }) g2 c0 ?& `Neurologic evaluation showed deep tendon reflex 2+1 Y. M! e) S* T3 f: J
bilateral and symmetrical. There was no suggestion
# m, I0 Q1 B* O* R9 C. A0 }0 U2 Hof papilledema." f* N" S8 o4 v/ O
Laboratory Evaluation
5 p, G$ T" [) ?& O* H% J3 }The bone age was consistent with 28 months by
" E7 z b# Q* C. J& K" Ousing the standard of Greulich and Pyle at a chrono-
& C e3 i$ g7 |logic age of 16 months (advanced).5 Chromosomal
/ P2 i6 ^8 Y2 j* o4 ikaryotype was 46XY. The thyroid function test
' K. V# A% f1 Z, cshowed a free T4 of 1.69 ng/dL, and thyroid stimu-
0 w1 w2 G! x) i4 s( \: Plating hormone level was 1.3 µIU/mL (both normal).
# _# E% m, ~( P; H( [$ O) \The concentrations of serum electrolytes, blood- L9 n7 |2 F( Y" }* g
urea nitrogen, creatinine, and calcium all were
) S, u( Z& N3 x) S: owithin normal range for his age. The concentration
! o; m+ N# E6 w. l Cof serum 17-hydroxyprogesterone was 16 ng/dL+ e. i" S( a5 r
(normal, 3 to 90 ng/dL), androstenedione was 20
?; @: j3 g/ Z; S S) z. ang/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
. c$ G1 Y5 M$ W: z7 ?terone was 38 ng/dL (normal, 50 to 760 ng/dL),
9 E& U7 l, _% v8 @ ydesoxycorticosterone was 4.3 ng/dL (normal, 7 to e* x1 Y, L6 v4 A3 i
49ng/dL), 11-desoxycortisol (specific compound S)0 c: ^+ C# |8 y1 j- p- v
was 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-9 o$ h' |; u3 V2 U* P
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total; i' U) K6 M. B, ?
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),9 H1 a$ i4 J/ K# S5 O. Q$ B- |) {
and β-human chorionic gonadotropin was less than
7 i* k- i, t9 L6 E5 mIU/mL (normal <5 mIU/mL). Serum follicular' f9 a8 p- g- U: r; P2 }& B
stimulating hormone and leuteinizing hormone, n$ [; ^ \- C7 o+ j3 c
concentrations were less than 0.05 mIU/mL' O% t H3 t9 E$ u
(prepubertal).
( s! A) `1 [/ I; H& t' T' @2 ]The parents were notified about the laboratory5 z- V: [9 c8 W- f+ j- V
results and were informed that all of the tests were$ v5 o4 X0 q4 f1 ?5 q/ T
normal except the testosterone level was high. The
1 e" e: x; Q. C/ Sfollow-up visit was arranged within a few weeks to) |1 v5 b+ `& y8 ^! ^3 J1 f6 w0 G; O
obtain testicular and abdominal sonograms; how-
- e& n9 r/ g: Oever, the family did not return for 4 months.' v% s, f& }# h9 Z' N6 m
Physical examination at this time revealed that the
0 Q9 y9 [+ D# D+ l0 \5 s$ ]1 rchild had grown 2.5 cm in 4 months and had gained4 z, F& ^& C$ o. h$ N! P% p
2 kg of weight. Physical examination remained
$ b& y8 R4 B. p: O$ bunchanged. Surprisingly, the pubic hair almost com-5 P! {' I, B: g ^8 R5 j, w
pletely disappeared except for a few vellous hairs at
9 [" Z% e- B5 F; b$ u5 R% Ythe base of the phallus. Testicular volume was still 20 m; I! O# ~2 Z
mL, and the size of the penis remained unchanged.
, J7 w( a8 f0 Z4 S& m% @The mother also said that the boy was no longer hav-6 V) e( D- n% R1 ~, B' j: E/ W; p
ing frequent erections.0 N9 y0 z* ~; N) w
Both parents were again questioned about use of( U% w; j$ g1 h9 N) R
any ointment/creams that they may have applied to
5 H F: o' z. Y0 cthe child’s skin. This time the father admitted the; c4 p: o2 S+ p& L3 X7 g9 C' M' q
Topical Testosterone Exposure / Bhowmick et al 541
+ _' L' X1 x! \. [3 q6 a7 i+ z+ u4 puse of testosterone gel twice daily that he was apply-2 }9 e. {$ z+ _& C
ing over his own shoulders, chest, and back area for7 m, I6 a$ v6 Z. O/ `7 V
a year. The father also revealed he was embarrassed
3 I# V, ^7 X- l j! Uto disclose that he was using a testosterone gel pre-2 |9 K: ~. o* n8 j4 N
scribed by his family physician for decreased libido
) a/ I/ t# ? p) f7 o7 Tsecondary to depression.
. k; `0 v$ s, o3 bThe child slept in the same bed with parents.3 V( f0 }# E/ o: U- Z
The father would hug the baby and hold him on his. Q; [5 s% ~# S5 H: g+ j
chest for a considerable period of time, causing sig-
6 ]1 y$ p* ]1 K8 l, inificant bare skin contact between baby and father.
+ E5 r2 l4 ^$ b# b3 ?' qThe father also admitted that after the phone call,
+ J6 o. \" V! Z/ x; J- ^when he learned the testosterone level in the baby* B H+ B, C: m8 I/ A
was high, he then read the product information
- _' k! l* P; Y* X0 ppacket and concluded that it was most likely the rea-7 S# a. |# X$ e. e, ^/ |! u7 V
son for the child’s virilization. At that time, they( A9 @8 q& A8 x) N- _+ H
decided to put the baby in a separate bed, and the0 i& a5 k/ i0 ^2 e' [: S% w
father was not hugging him with bare skin and had5 O q2 G8 h" x% Y8 z7 u
been using protective clothing. A repeat testosterone
' b5 b; Y& t% G6 o# K! ktest was ordered, but the family did not go to the2 g& g! G3 ?& C8 d. o
laboratory to obtain the test.% B8 `$ z2 q9 A: s
Discussion
; H! l, w' O+ nPrecocious puberty in boys is defined as secondary+ b/ P3 s$ ^% [8 f/ ^
sexual development before 9 years of age.1,4) C- j3 W! x( |5 r8 W5 F$ S! W
Precocious puberty is termed as central (true) when1 E( _+ t1 b2 ^
it is caused by the premature activation of hypo-
* F, R8 U3 H. U6 _7 h4 Bthalamic pituitary gonadal axis. CPP is more com-% G+ V9 H H6 Z2 ?; W! N, c
mon in girls than in boys.1,3 Most boys with CPP
/ q* j- [5 T4 u" |5 P+ t" k. bmay have a central nervous system lesion that is
# P! B2 Y g- |1 }' Lresponsible for the early activation of the hypothal-: O! y6 X$ l7 C
amic pituitary gonadal axis.1-3 Thus, greater empha-
. i2 y3 O' ~2 ~" G4 L9 Msis has been given to neuroradiologic imaging in
9 T1 t* K y9 b% C9 x2 |( Iboys with precocious puberty. In addition to viril-& @! a( L: M9 y' ^6 w( K$ q
ization, the clinical hallmark of CPP is the symmet-9 c7 `' f) a+ n0 [. X1 b
rical testicular growth secondary to stimulation by: S& g0 _% H) D1 r
gonadotropins.1,32 ^ w- I0 r; P4 I0 n0 H5 G
Gonadotropin-independent peripheral preco-. U8 F- m% }: Y
cious puberty in boys also results from inappropriate# n' J) z1 }$ i- a9 Q8 n
androgenic stimulation from either endogenous or
1 s6 Y& [" L2 [$ Eexogenous sources, nonpituitary gonadotropin stim-
: o5 J5 X* m8 ~0 v; P. _" |ulation, and rare activating mutations.3 Virilizing
1 p% n: R3 m" h* y; y3 _congenital adrenal hyperplasia producing excessive% b( B* p: c8 r& o7 e& }' d/ }
adrenal androgens is a common cause of precocious
z. J. d+ ~0 `4 _* Lpuberty in boys.3,4# @- U8 M) o, s3 g R# l
The most common form of congenital adrenal
: j: i$ L a0 l1 ~# q7 Ahyperplasia is the 21-hydroxylase enzyme deficiency.6 |/ Q; D$ N) j7 }4 G1 |
The 11-β hydroxylase deficiency may also result in
, G: D5 F+ W6 u# wexcessive adrenal androgen production, and rarely,( n/ Q+ Y; N x0 h7 { S K
an adrenal tumor may also cause adrenal androgen& {% k$ @6 L0 N3 o
excess.1,3( B; e4 Z7 Y" y/ V
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
5 ^0 s1 j- U( s& w, M( p542 Clinical Pediatrics / Vol. 46, No. 6, July 2007# O/ C8 u' R& X( h
A unique entity of male-limited gonadotropin-- q: R( i* T& Q4 }3 ^; a2 X
independent precocious puberty, which is also known) m: x+ Z. A6 p% q: P
as testotoxicosis, may cause precocious puberty at a
% M2 G2 I/ f7 t1 c/ g, hvery young age. The physical findings in these boys
. m9 n* K$ a/ T8 kwith this disorder are full pubertal development,
7 O; t3 u3 j; R7 J; @ Y7 H- Rincluding bilateral testicular growth, similar to boys
: v0 L# @: A f5 Nwith CPP. The gonadotropin levels in this disorder
5 _ F4 O" ?0 h" e& Q% @- @are suppressed to prepubertal levels and do not show
! Y& y& M% z3 r# j& N8 H+ ]pubertal response of gonadotropin after gonadotropin-" N- u* v, @; v y
releasing hormone stimulation. This is a sex-linked
$ |9 o% K1 w3 u1 Bautosomal dominant disorder that affects only' x5 F8 v8 W" ?/ [* l/ S
males; therefore, other male members of the family+ N+ ]' K) D; s j7 Q
may have similar precocious puberty.3
: R. ?+ |/ n" y, Y5 x7 O4 }) F b1 nIn our patient, physical examination was incon-
& i( {1 o y3 F' I/ x* y" c% Usistent with true precocious puberty since his testi-; D2 C* a: V- |- x% k! X
cles were prepubertal in size. However, testotoxicosis i: D, l1 D, O, b
was in the differential diagnosis because his father7 v" y+ f" D8 N4 e# H
started puberty somewhat early, and occasionally,
1 ~! b( o x1 Dtesticular enlargement is not that evident in the3 b/ S2 E' ]! s+ _1 J# w% e
beginning of this process.1 In the absence of a neg-/ y# M% l& U' v7 _2 d1 z
ative initial history of androgen exposure, our
9 G: Y5 S# u- R' p5 o7 b5 o3 \3 G2 Kbiggest concern was virilizing adrenal hyperplasia,- E8 \- f9 a. a, @8 s& Z' \
either 21-hydroxylase deficiency or 11-β hydroxylase1 }! }4 W; b' g* i0 w$ X+ T
deficiency. Those diagnoses were excluded by find-( y3 I8 u, I, s! E
ing the normal level of adrenal steroids.2 A S s- ?6 y6 D+ ]' e: V
The diagnosis of exogenous androgens was strongly
- @& w( B2 R7 b+ z& t& {1 Rsuspected in a follow-up visit after 4 months because
1 Z; Z- J; Z# Z8 c) V" ethe physical examination revealed the complete disap-
F# ^7 I3 Z5 K4 Jpearance of pubic hair, normal growth velocity, and7 L: } G+ C* z6 u6 h
decreased erections. The father admitted using a testos-1 S& C9 W \8 p: W9 \4 w" O
terone gel, which he concealed at first visit. He was
1 c: H% b0 _4 j0 O+ I. B) Z; fusing it rather frequently, twice a day. The Physicians’
7 C8 W- U5 C. E& `5 y0 Z3 QDesk Reference, or package insert of this product, gel or; l& m, b; g2 k, V2 W3 a- u0 }) [
cream, cautions about dermal testosterone transfer to
6 y- ~* |$ Y4 cunprotected females through direct skin exposure.
7 J F2 v. r1 M0 @& V4 d, ~9 QSerum testosterone level was found to be 2 times the! @4 S' e& X' r5 ~+ v( ^
baseline value in those females who were exposed to; t" t* F/ d+ Y; [8 }! r
even 15 minutes of direct skin contact with their male
0 N+ m/ q* C# P2 N G: C7 @, Upartners.6 However, when a shirt covered the applica-0 t8 @5 D' _. ^. `
tion site, this testosterone transfer was prevented.
! O7 u2 d c2 j/ xOur patient’s testosterone level was 60 ng/mL,! n* e _( r0 ~. e1 l! v4 Y( P
which was clearly high. Some studies suggest that! G! ]: O- K- a
dermal conversion of testosterone to dihydrotestos-
4 y/ i9 M6 o$ D E: ^terone, which is a more potent metabolite, is more. A# @. A& ]% H. W+ F. @, a7 \1 A0 e
active in young children exposed to testosterone
, W# n; Z8 i. J# ~exogenously7; however, we did not measure a dihy-% t& h2 V6 i" U+ A! K( F' p% u: M
drotestosterone level in our patient. In addition to
. z; y& I$ d6 e- r8 J7 k% ivirilization, exposure to exogenous testosterone in
3 d# g: H1 ~$ Ichildren results in an increase in growth velocity and
& B$ v1 T9 t* u, U/ t9 N# Eadvanced bone age, as seen in our patient.
# p; f8 {* O$ ~; w. w; x. uThe long-term effect of androgen exposure during; e8 F9 r C8 G
early childhood on pubertal development and final
: X5 @, A! n, D. x" m& A) w; vadult height are not fully known and always remain' ~* t0 @, r7 G: e- h1 }
a concern. Children treated with short-term testos-
+ B, n, W7 C6 {% t: l2 y9 w0 ^terone injection or topical androgen may exhibit some
0 @$ @1 m" e4 [* oacceleration of the skeletal maturation; however, after
2 O2 ]9 a3 c( X4 `; N. j% k9 Mcessation of treatment, the rate of bone maturation
- O! U4 D+ W' K: X! l7 adecelerates and gradually returns to normal.8,9
2 w( _ M+ [# I3 ^) V) bThere are conflicting reports and controversy
2 p7 y3 F7 m0 f& p, v1 Y ?0 \. L" z( {over the effect of early androgen exposure on adult
" v' m& k& q& ~ e+ J4 ?: tpenile length.10,11 Some reports suggest subnormal7 Z8 n L- ~+ O( i
adult penile length, apparently because of downreg-
9 Z- }2 t! O2 S0 D6 @1 bulation of androgen receptor number.10,12 However,
9 r- S, Z4 v: U3 w0 g4 p* PSutherland et al13 did not find a correlation between" Y% C2 B5 H6 m6 L
childhood testosterone exposure and reduced adult
O! V- v" q- Z- ^* Jpenile length in clinical studies.
% n! L4 q" o7 L9 l; N1 lNonetheless, we do not believe our patient is
1 Y+ Z0 Z* C7 K( \going to experience any of the untoward effects from
+ g4 n$ h% O1 z* h! `. M% M4 {' ?testosterone exposure as mentioned earlier because
- ?+ H' n) Q/ l6 Bthe exposure was not for a prolonged period of time.
& e9 k3 U; P$ w# z" x# |Although the bone age was advanced at the time of7 ^. h L- x g/ @
diagnosis, the child had a normal growth velocity at
4 O9 b# r4 E: N& T) @the follow-up visit. It is hoped that his final adult
; N& I! H* y( L2 |; e2 `1 Uheight will not be affected.
- d2 x; }: t) G" N IAlthough rarely reported, the widespread avail-
o& O8 }# x9 f" p# H# kability of androgen products in our society may
2 o7 q& O7 d# b+ L2 [ r( d* [indeed cause more virilization in male or female
- {# H! }- b/ x( a9 N; q, {1 Tchildren than one would realize. Exposure to andro-
) h; j& @4 E" K8 U3 J% jgen products must be considered and specific ques-
8 k4 f" I4 W: t% @! f' a. E; `tioning about the use of a testosterone product or. N2 H4 c# I# O# P+ z% K# K, T
gel should be asked of the family members during
; `) }: V" ^5 `% [the evaluation of any children who present with vir-
- U, \. d" x, }; H( A; Hilization or peripheral precocious puberty. The diag-
2 `) S; B# o" h6 A8 mnosis can be established by just a few tests and by
( A0 I! L. r+ I1 Sappropriate history. The inability to obtain such a
& O" {3 g6 l; e! c5 U- qhistory, or failure to ask the specific questions, may' F/ ^ g) J5 [( Y
result in extensive, unnecessary, and expensive
8 H; [! D3 ~: R0 c/ b7 zinvestigation. The primary care physician should be" _2 g; ?9 g0 P1 _- R
aware of this fact, because most of these children! T# R7 A) @5 h
may initially present in their practice. The Physicians’
- C" F2 G! f3 t2 VDesk Reference and package insert should also put a
; l; _+ j! C3 w2 }warning about the virilizing effect on a male or
# q# h! k7 a4 @5 t& cfemale child who might come in contact with some-5 a1 b* m7 j+ l5 Q: E3 l" b
one using any of these products.: w' N& }) j4 X+ u8 K
References; e5 V+ Q5 D2 Y' g4 h
1. Styne DM. The testes: disorder of sexual differentiation
8 z0 @: ~* A% s V, W$ `and puberty in the male. In: Sperling MA, ed. Pediatric
0 p* G9 B% C9 P3 V6 ZEndocrinology. 2nd ed. Philadelphia, PA: WB Saunders;
) j- w8 U- I+ R+ y2002: 565-628.
/ {" N( Q6 F) D, ` y! d" N2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
]2 ~) M( L# P" m3 e. L1 E" zpuberty in children with tumours of the suprasellar pineal |
|