Fig. 1Relapse-free survival of Graves disease patients after antithyroid drug withdrawal in the thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) groups. Among 74 patients, there was no significant difference in the relapse-free survival between the TSAb and TBII groups.
Fig. 2Relapse-free survival of the patients after antithyroid drug (ATD) withdrawal in the thyroid stimulatory antibody (TSAb) group according to TSAb levels. At ATD withdrawal using a cut-off value of (A) 140%, (B) 130%, (C) 160%, and (D) at 3 months after ATD withdrawal.
Fig. 3Relapse-free survival of the patients after antithyroid drug (ATD) withdrawal in the thyrotropin-binding inhibitory immunoglobulin (TBII) group according to TBII levels. At ATD withdrawal using a cut-off value of (A) 1.5, (B) 1.0, (C) 2.0, and (D) at 3 months after ATD withdrawal.
Fig. 4Distribution of thyroid stimulatory antibody (TSAb) titers in patients with remission and Graves disease relapse. The medians of the TSAb titers were 61.1% and 203.5% in patients with remission and relapse, respectively (dotted lines).
Table 1Baseline Characteristics of the Graves Disease Patients in the TSAb and TBII Groups
Characteristic |
Total (n=74) |
TSAb group (n=35) |
TBII group (n=39) |
P value |
Age at diagnosis, yr |
31.5±13.2 |
39.1±14.4 |
43.6±11.8 |
0.14 |
Female sex |
56 (76) |
24 (69) |
32 (82) |
0.18 |
Presence of a goiter |
41 (55) |
18 (51) |
23 (59) |
0.51 |
Small (<40 g) |
24 (32) |
11 (31) |
13 (33) |
0.77 |
Medium to large (≥40 g) |
17 (23) |
7 (20) |
10 (26) |
|
Family history of Graves disease |
2 (3) |
1 (3) |
1 (3) |
0.99 |
Thyroid associated orbitopathy |
10 (14) |
6 (17) |
4 (10) |
0.50 |
Antithyroid drug |
|
|
|
|
Methimazole |
58 (78) |
28 (72) |
30 (86) |
|
Carbimazole |
9 (12) |
6 (15) |
3 (9) |
0.16 |
Propylthiouracil |
7 (9) |
5 (13) |
2 (6) |
|
Treatment duration of ATD, mo |
22.0 (16.0-26.5) |
24.0 (18.0-32.0) |
21.0 (16.0-26.0) |
0.19 |
Euthyroid duration of ATD, mo |
10.5 (5.0-17.5) |
10.4 (9.9-13.4) |
10.6 (9.0-14.0) |
0.67 |
Thyroid function test at diagnosis |
|
|
|
|
Total T3, nmol/L |
4.5±1.9 |
4.3±1.2 |
4.6±2.3 |
0.55 |
Free T4, pmol/L |
38.6±16.7 |
38.6±15.4 |
38.6±18.0 |
0.95 |
TSH, mIU/L |
0.05±0.02 |
0.04±0.01 |
0.06±0.03 |
0.02 |
Thyroid function test at ATD withdrawal |
|
|
|
|
Total T3, nmol/L |
2.2±0.3 |
2.2±0.3 |
2.2±0.3 |
0.92 |
Free T4, pmol/L |
16.7±2.6 |
18.0±2.6 |
16.7±2.6 |
0.07 |
TSH, mIU/L |
2.7±3.1 |
2.3±1.9 |
3.2±3.8 |
0.22 |
Positivity of TSAb or TBII |
23 (31) |
12 (34) |
11 (28) |
0.87 |
Follow-up duration, mo |
21.0 (10.0-27.5) |
15.0 (10.0-23.0) |
22.0 (9.0-34.0) |
0.05 |
Relapse |
28 (38) |
12 (34) |
16 (41) |
0.55 |
Table 2Clinical Factors in TRAb-Positive and -Negative Patients in the TSAb and TBII Groups
Variable |
TSAb (n=35) |
TBII (n=39) |
Negative (n=23) |
Positive (n=12) |
P value |
Negative (n=28) |
Positive (n=11) |
P value |
Age at diagnosis, yr |
40.3±15.2 |
37.7±13.0 |
0.49 |
43.4±12.0 |
44.2±11.6 |
0.86 |
Female sex |
15 (65) |
9 (75) |
0.71 |
22 (79) |
10 (91) |
0.65 |
Presence of a goiter |
13 (57) |
5 (42) |
0.40 |
16 (57) |
7 (64) |
0.99 |
Small (<40 g) |
10 (43) |
1 (8) |
0.05 |
10 (36) |
3 (27) |
0.65 |
Medium to large (≥40 g) |
3 (13) |
4 (33) |
0.05 |
6 (21) |
4 (36) |
0.65 |
Family history of Graves disease |
1 (4) |
0 |
0.99 |
1 (4) |
0 |
0.99 |
Thyroid-associated orbitopathy |
4 (17) |
2 (17) |
0.99 |
3 (11) |
1 (9) |
0.99 |
Antithyroid drug |
|
|
|
|
|
|
Methimazole |
18 (78) |
12 (100) |
|
17 (61) |
11 (100) |
|
Carbimazole |
3 (13) |
0 |
0.11 |
6 (21) |
0 |
0.03 |
Propylthiouracil |
2 (9) |
0 |
|
5 (18) |
0 |
|
Treatment duration of ATD, mo |
22.0 (18.0-32.0) |
25.0 (17.0-31.3) |
0.99 |
21.0 (14.5-25.8) |
22.0 (16.0-28.0) |
0.81 |
Euthyroid duration of ATD, mo |
10.3 (9.9-24.0) |
10.5 (9.8-13.8) |
0.66 |
10.6 (9.6-14.6) |
10.6 (10.0-20.7) |
0.30 |
Thyroid function test at diagnosis |
|
|
|
|
|
|
Total T3, nmol/L |
4.3±1.0 |
4.3±1.6 |
0.96 |
4.6±2.3 |
4.7±2.2 |
0.92 |
Free T4, pmol/L |
41.2±16.7 |
36.0±14.2 |
0.55 |
38.6±16.7 |
41.2±23.2 |
0.70 |
TSH, mIU/L |
0.04±0.01 |
0.04±0.004 |
0.42 |
0.06±0.03 |
0.05±0.02 |
0.76 |
Thyroid function test at ATD withdrawal |
|
|
|
|
|
|
Total T3, nmol/L |
2.2±0.3 |
2.3±0.4 |
0.14 |
2.2±0.3 |
2.2±0.3 |
0.63 |
Free T4, pmol/L |
16.7±2.6 |
19.3±2.6 |
0.01 |
16.7±2.6 |
15.4±2.6 |
0.21 |
TSH, mIU/L |
2.4±2.0 |
1.9±1.6 |
0.41 |
3.0±2.7 |
3.6±7.1 |
0.69 |
TSAb or TBII levelsa
|
63.9±36.9 |
323.8±146.1 |
<0.05 |
0.8±0.4 |
3.7±3.5 |
<0.05 |
Follow-up duration, mo |
20.0 (11.0-24.0) |
13.0 (5.5-20.3) |
0.14 |
22.0 (10.3-34.8) |
23.0 (7.0-27.0) |
0.49 |
Relapse |
4 (17) |
8 (67) |
0.01 |
12 (43) |
4 (36) |
0.99 |
Table 3Diagnostic Values of TSAb and TBII at Antithyroid Drug Withdrawal for Hyperthyroidism Relapse in Patients with Graves Disease
Vaiable |
TSAb (n=35) |
TBII (n=39) |
Negative (n=23) |
Positive (n=12) |
Negative (n=28) |
Positive (n=11) |
Relapse |
4 (17) |
8 (67) |
12 (43) |
4 (36) |
Diagnostic values, % |
|
|
Sensitivity |
63 |
28 |
Specificity |
83 |
65 |
Negative predictive value |
78 |
45 |
Positive predictive value |
69 |
47 |
Accuracy |
76 |
50 |
Table 4Cox Proportional Hazard Modeling for Predicting Graves Disease Relapse in the TSAb Group
Variable |
|
Univariate |
|
|
Multivariate |
|
HR |
95% CI |
P value |
HR |
95% CI |
P value |
Age at diagnosis, yr |
0.99 |
0.95-1.03 |
0.65 |
- |
- |
NA |
Male sex |
1.04 |
0.31-3.47 |
0.06 |
- |
- |
NA |
Goiter (medium to large) |
2.07 |
0.62-6.94 |
0.24 |
- |
- |
NA |
Thyroid associated orbitopathy |
1.14 |
0.24-5.41 |
0.87 |
- |
- |
NA |
Severe hyperthyroidism at diagnosisa
|
1.63 |
0.20-13.39 |
0.65 |
- |
- |
NA |
Treatment duration of ATD |
1.00 |
0.99-1.02 |
0.85 |
- |
- |
NA |
Positive TSAb levels at ATD withdrawalb
|
5.21 |
1.53-17.71 |
0.008 |
6.68 |
1.29-34.62 |
0.02 |