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NGHIN CU MT S C IM LM SNG XT NGHIM,

KHNG TH KHNG TH TH TSH BNH NHN BASEDOW


TRC V SAU IU TR 131I
Bi Thanh Huyn
Bnh vin Ni tit Trung ng
Study of clinical and laboratory
characteristics and TSH receptor
antibody in patients with graves disease
Basedow disease is the most
frequent thyroid disorder with the
symptoms
of
hyperthyrodism,
exophthalmos and swelling of thyroid
gland, caused by stimulating the thyroid
antibodies against the TSH receptor.
There is a closely correlation between the
concentration of TRAb and exophthalmos
in Bassedows disease. The euthyroid or
hyperthyroid state obtained after treating
with I311 is correlated to the concentration
of the concentration of TRAb. Mesurement
of serum TRAb level is of value in
diagnosis, follow up and prediction of
disease outcome in Basedow patients who
received treatment with I311. The purpose
of this study is to evaluate the changes in
serum TRAb level in Basedow patients
before and after treatment with I311

Tm tt
Basedow l mt bnh tuyn
gip thng gp vi cc triu chng
cng gip, li mt, bu gip lan
to, gy ra bi khng th khng th
th TSH. C mt mi lin quan cht
ch gia nng ca khng th ny
v triu chng li mt trong bnh
Basedow. T l bnh nhn bnh gip
hay cn cng gip sau iu tr 1311
c lin quan vi nng TRAb cao
hay thp. Nng TRAb trong huyt
tng c gi tr trong chn on,
theo di v tin lng bnh
Basedow sau iu tr bng I311.
Trong nghin cu ny, chng ti
nh gi s thay i ca nng
TRAb trn nhng bnh nhn
Basedow trc v sau khi iu tr
bng I311.

T VN
Basedow l mt bnh ni tit thng gp nc ta cng nh trn th gii.
Basedow c xp vo loi bnh c c ch t min dch.
Hin nay c 3 phng php iu tr c bn l:
- iu tr ni khoa bng thuc khng gip trng tng hp (KGTTH)
- iu tr bng phu thut ct b tuyn gip
- iu tr bng iod phng x (131I)
Nm 1978 ln u tin 131I c p dng iu tr Basedow ti khoa Y hc ht
nhn Bnh vin Bch Mai
n nay, trong c nc c hng ngn bnh nhn Basedow c iu tr bng
131
I . Trn th gii cng nh nc ta c kh nhiu nghin cu v hiu qu cng
nh cc bin chng ca vic s dng 131I trong iu tr bnh cng gip ni chung v
bnh Basedow ni ring.

nc ta nghin cu v ng dng 131I trong iu tr Basedow c nhiu nhng


nhng nghin cu TRAb bnh nhn Basedow trc v sau iu tr 131I cha c.
Mc tiu nghin cu:
1. Phn tch mt s c im lm sng, cn lm sng bnh nhn Basedow
trc v sau iu tr 131I.
2. Xc nh nng TRAb ngi bnh thng, bnh nhn Basedow trc v
sau iu tr 131I.
3. Bc u kho st s thay i nng TRAb, t l TRAb dng tnh (+) v
TRAB m tnh (-) cc bnh nhn b cng gip ti pht, suy gip v tr v
bnh gip sau iu tr 131I.
2. I TNG V PHNG PHP NGHIN CU
2.1. i tng nghin cu.
+ Ngi bnh thng trng thnh (nhm chng): 46 ngi.
+ Bnh nhn c chn on xc nh l bnh nhn
Basedow trc v sau iu tr 131I: 64 bnh nhn.
2.2. Phng php nghin cu.
2.2.1. La chn bnh nhn.
+ Ch nh: nhng bnh nhn c chn on xc nh
l Basedow c ch nh iu tr bng 131I
2.2.2 Cc tiu chun chn on v nh gi.
Da vo mt s triu chng lm sng v cn lm sng
2.2.3. Cch tnh liu phng x v cch dng.
+ Liu iu tr 131I cho bnh nhn Basedow c tnh theo
cng thc sau:
C.P
131
Liu I (mCi) = ----------x 100
T24
Trong :
C l s mCi cho 1g t chc tuyn gip (t 0,08-0,15 mCi/g
tuyn gip)
P: Trng lng tuyn gip (g) c xc nh qua s nn v siu
m tuyn gip.
T24: tp trung 131I ti tuyn gip sau 24h.
+ Thuc phng x 131I
+ Cch dng:
- Liu 131I mi bnh nhn c tnh ton v o hot tnh
phng x trn my o liu Calibrator ca M sn xut.
- Bnh nhn c ung 131I trc ba n (khi i) 2 gi sau khi
ung, bnh nhn c th n ung bnh thng.
2.2.4. Theo di sau iu tr v nhn nh kt qu.
* Theo di sau iu tr:

- Sau khi nhn liu iu tr 131I s c nm ti khoa Y hc ht


nhn, Bnh vin Bch Mai t 3-5 ngy
- Sau 3 thng, 6 thng, 1 nm, 2 nm bnh nhn c gi tr li
khm
* nh gi kt qu iu tr:
+ Kt qu tt (khi bnh)
+ Cn cng gip
+ Suy gip:
2.2.5. nh lng TRAb.
+ Ho cht: s dng b kit RIA - TRAb ch sn ca hng CIS bio
interanational (ca Php), thnh phn gm:
- TSH nh du phng x 125I - TSH
- Khng nguyn chun khng nh du phng x vi cc
nng cho trc:
0, 5, 15, 45, 135, 405 U/l
- TSH receptor
- Cc l Control cho trc nng kim tra (Control I ,
II)
- Dung dch m (buffer) ...
- Dung dch gy ta
+ Dng c v my:
o hot tnh phng x cc mu, x l tnh ton cc mu o
bng my t ng Okfil - ca Anh v chng trnh x l s liu ca
WHO dnh ring cho RIA (WHO immuno D.P. Program)
Bng 1. Cc bc tin hnh nh lng TRAb (n v th tch l
l)
Huyt
S1 Contr thanh
TC
NSB
So
olI&II
bnh
S5
nhn
So
50
50
50
S1 S5
HT bnh nhn
50
TSH receptor
50
50
50
50
Control receptor
Trn v
15 pht 20 - 250C
125
I - TSH
100 100 100
100
100
100
Trn v
2 gi 20 - 250C
Dung dch gy ta
200 200 200
200
200
200
Trn ly tm, b
30 pht 2 - 80C (1500 g)
dch trong
m hot tnh phng
2 pht
x
Ghi ch: TC: total count ; NSB: non specific binding

S0

S5

: standard0

standard5

2.2.6. X l s liu.
S liu c s l theo chng trnh EPI INFO 6.0 v SPSS ca M.
2.2.7. Ni tin hnh nghin cu.
Bnh vin Ni Tit trung ng v khoa Y hc ht nhn Bnh vin Bch Mai.
3. KT QU V BN LUN
3.1. Tnh hnh bnh nhn Basedow trc iu tr 1311:
- Tng s bnh nhn c iu tr l 64.
- Tui trung bnh 46,9 11,13
- Gii: n > nam (47/64) 73,4%
- Cc triu chng lm sng v cn lm sng khng c g khc bit ln so vi
mt s tc gi Phan S An, Phan Vn Duyt, Trn nh Ngn v Harbezt J.C.
3.2. bin i mt s triu chng lm sng v cn lm sng bnh nhn Basedow
trc v sau iu tr
Bng 2. So snh nhp tim trc v sau iu tr 6- 24 thng ( n = 46) .
Ch s thng k

Trc iu tr

Sau iu tr
3-5 thng

Sau iu tr
6-24 thng

Nhp tim (TB SD)


(ln/pht)

102,2 13,7

84,3 13,5*

77,6 7,9**

*: p < 0,001 so snh trc iu tr vi sau iu tr 3-5 thng


**: p < 0,001 so snh trc iu tr vi sau iu tr 6-24 thng

Bng 3. Thay i v t bo mu sau 6-24 thng iu tr.


Trc iu tr

Sau iu tr 6-24thng

(X SD)

(X SD)

Hng cu
(tb/mm3)

4.696.000 512.000
n=42

4.871.000 409.400
n=21

> 0,05

Bch cu
(tb/mm3)

6.535 1.498
n=60

6.519 1.313
n=23

> 0,05

Bch cu NTT
(nghn/mm3)

4.156 1.303
n=60

3.940 908
n=22

> 0,05

Xt nghim

Cc t bo mu trc v sau iu tr thay i khng c ngha thng k


(p>0,05)
Bng 4: Mt s thay i v cn lm sng cc bnh nhn Basedow sau iu tr
131
I 3-24 thng
Sau iu tr
Xt nghim
Trc iu tr
p
6-24 thng
33,1 12,0
17,5 4,6
Th tch TG (ml)
< 0,001
n = 62
n 22

40,4 18,3
14,5 7,2
< 0,001
n = 64
n = 15
83 12,2
31,4 14,7
tp trung 131I sau 24h (%)
< 0,001
n = 64
n = 15
Nng T3 huyt thanh
4,2 2,26
2,13 0,94
< 0,001
(nmol/l)
n = 64
n = 39
270,37
Nng T4 huyt thanh
85,20 57,73
< 0,001
102,17
(nmol/l)
n = 13
n = 36
Nng FT3 huyt
63,56 43,45
15,83 19,88
< 0,05
thanh(pmol/l)
n = 27
n=5
Nng TSH huyt
0,048 0,046
10,58 18,642
< 0,001
thanh(mU/l)
n = 64
n =39
- TG nh i so vi trc iu tr 33,1 12,0ml so vi 17,5 4,6ml (p< 0,001)
ph hp vi cc tc gi Phan Vn Duyt, Phan S An v Hazberrt
3.3. Kt qu chung sau iu tr.
- Vi liu iu tr trung bnh: 6,33 1,34 mCi cho mt bnh nhn
- S ln iu tr 1,33 ln cho mt bnh nhn c 75% v bnh gip, 11,7% cn
cng gip 13,3% suy gip.
tp trung 131I sau 2h (%)

Bng 5: T l cn cng gip theo mt s tc gi


Tc gi
Phan S An v cs (1999)
Quch Vn Hin (1999)
Nguyn Vn T v cs (1999)
L Minh Thanh, (2000)
Bi Thanh Huyn

T l cng gip (%)


11,2
12
10,6
7
11,7

Bng 6: T l suy gip sau iu tr 131I theo mt s tc gi


Tc gi
T l suy gip (%)
Phan Vn Duyt, (1978)
13,8
Phan S An v cs (1999)
14,8
L Minh Thanh, (2000)
12
Bi Thanh Huyn
13,3
3.4. Nng TRAb ngi bnh thng v bnh nhn Basedow trc v sau iu tr
131
I.
3.4.1. Nng TRAb ngi bnh thng trng thnh.
Bng 7. Nng TRAb (U/l) trong mu ngi bnh thng theo gii.

SD
Median
Min-Max
Ql-Qu
X
Nam
24
2,08
1,86
2,28
0-9,20
1,33-2,54
N
22
3,01
2,87
2,28
0-10,15
1,80-2,90
Chung
46
2,52
2,42
2,28
0-10,15
1,35-2,89
Khng c s khng khc bit v nng TRAb gia nam v n (p>0,05). Nng
TRAb ngi trng thnh l 2,28U/l (Median); Min: 0U/l; Max: 10,15U/l; Q1:
1,35U/l; Qu: 2,89U/l.
Gi tr ln nht TRAb ngi bnh thng l 10,15 U/l theo hng CIs bio
international ( Php)
Chng ti chn ngng:
+ TRAb < 11U/l coi l (-)
+ v TRAb > 11U/l coi l (+)
Tng t gi tr ca Hng v mt s tc gi khc
Bng 8. Nng TRAb ngi bnh thng trng thnh
Gii

Tc gi

71
106

TRAb (U/l)
[TRAb (-): TRAb m tnh
< 15
< 14 (nh lng theo kit Dyno
test TRAb-assay Brahms)
< 2(nh lng theo kit TRAbhuman Brahms: siu nhy)
<2
<8
< 10

296

< 11

Paunkovic N.D v cs (2000)


Larbre H v cs (2000)

56

Massart C v CS (2000)
Shibayama K v cs 92000)
Pedersen B v cs (2000)
Hng C Bio International (Php)
(2002)

< 11
Bi Thanh Huyn v CS
46
Min: 0 ; Max: 10,15 ; Median:
2,28
Gii hn bnh thng TRAb trong mu ngi bnh thng khc nhau theo tu
tng tc gi, tu quc gia v phng xt nghim khc nhau. S khc bit ny ch yu
ph thuc vo phng php nh lng TRAb c nhy khc nhau>
3.4.2. Nng TRAb bnh nhn Basedow trc iu tr.
Bng 9. Nng TRAb (U/l), TRAb (+) v TRAb (-) bnh nhn Basedow trc khi iu tr 131I.
TRAb(U/l)

TRAb +(>11)

53

TRAb (<11)

X
452,8
1
6,37

SD

Median

Ql-Qu

87,94

457,63

425,44499,40

2,22

6,25

5,03-9,32

Min-Max

TRAb (+) v
344,8
2,3662
207,33 432,26 31,54-475,64
(-) (chung)
0
592,61
Trc iu tr TRAb cao gp hng trm ln so vi ngi bnh thng 457,63U/l
so vi 2,28U/l (Median) (p<0,0001)
Bng 10: T l TRAb (+) bnh nhn Basedow trc iu tr mt s tc gi.
Tc gi
n
TRAb (+) trc iu tr (%)
Aiawa Y (1995)
225
78% (126)/225)
Sato K. v cs (2000)
> 90%
Massart C. v cs (2000)
140
98,6%
Schifferdecker E. (1986)
53
94,3% (50/53)
Bi Thanh Huyn v cs
62
85,5% (53/62)
Kt qu nghin cu:
T l TRAB (+) l 85,5% v TRAb (-) l 14,5% (p< 0,0001)
Nhn xt trn ph hp vi Pedersen B., Laurbeg P., v csl Moagenthaler,
Phel Z
3.4.3.Nng TRAb bnh nhn basedow sau iu tr
Bng 11. So snh nng TRAb gia ngi bnh thng vi bnh nhn
Basedow trc v sau iu tr 131I.
TRAb
n
Median
Min-Max
Ql -Qu
a
Ngi bnh thng
46
2,28
0-10,15
1,35-2,89
b
Basedow trc iu tr
62
432,6
2,36-592,61 31,54-475,64
c
Basedow sau iu tr 3-5
60
49,92
1,80-93,21
9,20-93,21
thng
d
Basedow sau iu tr 6-24
58
8,71
0-19,31
5,21-19,31
thng
So snh:
a - b: P < 0,0001
b - c: P < 0,0001
a - c: P < 0,0001
b - d: P < 0,0001
a - d: P < 0,001
c - d: P < 0,001
Nng TRAb c xu hng gim dn khi thi gian sau iu tr tng ln.
Nhn xt trn ph hp vi Shfferdeckez E v cng s (1986)
Bng 12. T l % bnh nhn Basedow c TRAb (+) v ( -) trc v sau iu tr.
TRAb (+)
TRAb (-)
n
%
n
%
Trc iu tr
53
85,5
9
14,5
Sau iu tr 3-5 thng
45
75
15
25
Sau iu tr 6-24
19
32,7
39
67,3
thng
p
< 0,001
< 0,01

TRAb (+) tng cao trc iu tr v gim dn sau iu tr


TRAb (-) li tng dn t trc iu tr ti sau iu tr
So snh t l % bnh nhn Basedow c TRAb(+) v TRAB(-) trc v sau iu
tr.
TRAb(+)

(%)
80

TRAb(-)

70
60
50
40
30
20
10
0
Tr c iu tr

Sau 3-5 thng

Sau 6-12 thng

T l TRAb (-) v (+) c gi tr ln trong vic nh gi theo di


tin lng bnh nhn Basedow trc v sau iu tr
3.3.4. So snh t l % TRAB (+) v TRAb (-) trc v sau iu tr ca
bnh nhn cn cng gip, bnh gip v suy gip c 3 nhm bnh
nhn
Sau iu tr 131I 3-24 thng kt qu c 3 nhm bnh nhn: Cng gip, bnh gip v suy gip
Bng 13. Kt qu iu tr
Kt qu iu tr
Khi
Cn cng
gip
Suy gip

S bnh nhn

T l %

45

75,0

11,7

13,3

Nghin cu s bin i nng TRAb cc nhm cho thy:


Trc iu tr nhm cn cng gip c TRAb l cao nht thp hn
nhm bnh gip v thp nht nhm suy gip (p< 0,001)
Bng 14. So snh nng TRAb (U/l) trc v sau iu tr
bnh nhn Basedow cn cng gip, suy gip v bnh
gip sau iu tr
Trc iu tr
Sau iu tr
Bnh
P
Media
nhn
Median
X SD
X SD
n

Cng gip
ti pht
(n=7)
Bnh gip
(n=45)
Suy gip
(n=8)

532,87
50,84

541,34

29,73
10,18

35,78

410,99 109
,87

427,58

12,49
11,96

8,66

9,84 8,98

7,07

6,36 5,33

4,24

<0,0
01
<0,0
01
>0,0
5

Bng 15. So snh t l TRAb (+) v TRAb (-) trc v sau iu


tr ca bnh nhn Basedow cn cng gip ti pht, suy
gip v bnh gip sau iu tr 131I.
TRAb (+)
TRAb (-)
Bnh nhn Trc iu Sau iu Trc iu Sau iu
tr
tr
tr
tr
Cn cng
1/7(14,3
7/7(100%) 6/7(85,7%)
gip
%)
1/8(12,5%
7/8(87,5%
Suy gip
2/8(25%)
6/8(75%)
)
)
45/47(95, 10/45(22,2 2/47(4,3% 35/45(77,
Bnh gip
7%)
%)
)
8%)
Ph hp vi Schifferdeckez E., Schulz F., Ffling K., Chiovato L.,
Fiore., v cs.
- Trc iu tr:
+ 100% (7/7) bnh nhn cn cng gip sau iu tr c
TRAb(+)
+ T l ny 12,5% (1/8) nhm suy gip v 95,7% nhm
bnh gip
- Sau iu tr
+ Trc v sau iu tr nng TRAb c 3 nhm gim r
rt (P< 0,001).
+ Sau 3-24 thng iu tr nng TRAb gim c 3
nhm nhng nhm suy gip gim khng r
Ph hp vi cc tc gi Chivato L, Fiore E, Vitti P, v cs Smith R.
v cs
- T l TRAb (+) v (-) trc v sau iu tr thay i khng r
rt nhm cn cng gip v suy gip nhng rt r nhm bnh gip.
Ph hp vi tc gi Aizawa Y. v cs ; Yoshida K. v cs.
Nh vy:
- Nng TRAb cao, t l cao TRAb (+) trc iu tr l du
hiu quan trng cho tin lng kh nng ti pht sau iu tr.
- Nng TRAb thp, t l cao TRAb (-) trc iu tr l du
hiu tt
lu kh nng suy gip sau iu tr

4. KT LUN
4.1.Vi liu iu tr trung bnh l 6,32 1,3 mCi 131I v s ln iu tr trung bnh l
1,33 ln cho mt bnh nhn: c 75% (45/60) bnh nhn Basedow tr v bnh
gip, 11,7% (7/60) vn cn cng gip v ch c 13,3% (8/60) b suy gip trng. Thi
gian sau iu tr cng di, chc nng tuyn gip cng tr v n nh. Sau iu tr 6-24
thng, tnh trng cng gip c bn tr v bnh thng. Khng c s thay i v s
lng cc t bo mu trc v sau iu tr. Ring tnh trng li mt it c ci thin.
4.2. Nng TRAb ngi bnh thng trng thnh l: 2,28 U/l (Median), thp nht
l 0 U/l v cao nht l 10,15 U/l. Khng c s khc bit v nng TRAb gia nam
v n (p>0,05)
- Trc iu tr 131I, nng TRAb ca cc bnh nhn Basedow l 432,26 U/l
(Median), thp nht l 2,36 U/l v cao nht l 592,61 U/l. Nng ny cao gp hng
trm ln so vi ngi bnh thng (p<0,0001).
- Nng TRAb cao nht cc bnh nhn Basedow trc iu tr, sau gim
mnh khi thi gian sau iu tr tng ln t 49,92U/l (Median), sau 3-5 thng xung cn
8,71U/l (Median) sau 6-24 thng (p<0,0001).
- T l TRAb(+) trc iu tr l 85,5%, ri gim t 75% sau 3-5 thng xung
cn 32,7% sau 6-24 thng (p<0,001)
- T l TRAb(-) trc iu tr l 14,5% tng t 25% sau 3-5 thng iu tr ln
67,3% sau 6-24 thng (P<0,01)
- Nng TRAb trc iu tr c gi tr cao nht cc bnh nhn Basedow cn
cng gip, thp hn nhm bnh gip v thp nht nhm suy gip sau iu tr
(532,87 U/l so vi 410,99 U/l v 9,84 U/l) p<0,001.
- Sau iu tr nng TRAb nhm cng gip v bnh gip u gim i r rt
so vi trc iu tr (p<0,001), nhng thay i khng r nhm bnh nhn b suy gip
(p>0,05)
- Trc iu tr 100% (7/7) bnh nhn b cng gip sau iu tr c TRAb(+),
t l ny l 95,7% (45/47), nhm bnh gip v 12,5% (1/8) nhm suy gip sau iu
tr.
- T l TRAb(-) trc iu tr cao nht nhm suy gip (87,5%:7/8), thp hn
nhm bnh gip (4,3%:2/47), v thp nht (0%) nhm cn cng gip sau iu tr.
5. KIN NGH
Nng TRAb mc cao v t l cao TRAb (+) trc iu tr l mt du hiu
quan trng cho vic tin lng kh nng ti pht sau iu tr 131I cc bnh nhn
Basedow. Nhng bnh nhn Basedow c nng TRAb thp v t l TRAb (-) cao
trc iu tr l du hiu tt tin lng kh nng suy gip sau iu tr 131I. Do vy
nh lng nng TRAb l mt xt nghim cn c a vo thng quy trong chn
on, theo di bnh nhn Basedow.
TI LIU THAM KHO

1.

Phan S An., Phan Vn Duyt., Mai Trng Khoa v cs. (1999), Tng kt qua
20 nm iu tr bnh cng gip bng iod phng x131I ti khoa Y hc ht nhn
Bnh vin Bch mai, H Ni,Tp ch Y hc Vit Nam, S 8-9,Tr.68-71
2.
Trn Khnh D (1987), Bnh l ca tuyn gip, Nxb Tp H Ch Minh, Tr. 39
3.
ng Trn Du (1996), Bnh tuyn gip v cc ri lon do thiu iod, Nxb. Y
hc, H Ni, Tr. 451-489.
4.
Mai Trng Khoa (1996), Nghin cu bng phng php kim nh mim dch
phng x hm lng ni tit t T3, T4, TSH trong mt s iu kin bnh thng v
bnh l, Lun n PTS khoa hc Y dc, H Y H Ni, Tr. 28-30.
5.
Thi Hng Quang (1989), Bnh Basedow, Bnh Ni tit, Hc vin Qun Y,
Tr. 62-82.
6.
Trn c Th (1999), Bnh hc tuyn gip, Bi ging bnh hc, Nxb. Y hc,
H Ni, Tp 1, Tr. 246-273
7.
Mai Th Trch, Nguyn Thy Kh (1999), Ni tit hc i cng, i hc Y
dc thnh ph H Ch Minh, Tr. 204-291.

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