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Jurnal Hipertiroid
Jurnal Hipertiroid
Original
Advance Publication
doi: 10.1507/endocrj. K10E-262
Abstract. According to the guideline issued by the Japan Thyroid Association in 2006 for treatment of Graves disease,
discontinuing antithyroid drug (ATD) therapy is recommended when serum free thyroxine (FT4) and thyroid stimulating
hormone (TSH) concentrations have been maintained within the reference range for a certain period after treatment with
one ATD tablet every other day (minimum maintenance dose therapy, MMDT). In this retrospective study, the relationship
between MMDT duration and remission rate was investigated. The participants were 107 consecutive patients with Graves
disease whose ATD therapy was stopped according to the guideline. Serum FT4, TSH, and TSH receptor antibody (TRAb)
levels were measured when ATD was discontinued and every 3 months thereafter. The percentage of patients in remission
was 86.9% at 6 months, 73.8% at 1 year, and 68.2% at 2 years after ATD discontinuation. The remission rate increased
with MMDT duration, being significantly higher in patients with MMDT durations of 19 months or more than those with
MMDT durations of 6 months or less. In patients with MMDT durations of 6 months or less, the remission rate was
significantly lower in TRAb-positive patients than in TRAb-negative patients at the time of withdrawal of ATD; however,
this was not observed in patients with MMDT durations of 7 months or more. These findings suggest that in patients who
discontinue ATD after a certain MMDT duration, the remission rate increases as the MMDT duration increases, and ATD
should not be discontinued in TRAb-positive patients with MMDT durations of 6 months or less.
Key words: Graves disease, Antithyroid drug treatment, Drug discontinuation, TSH receptor antibody, Remission rate
Antithyroid drugs (ATDs) such as methimazole (MMI) and propylthiouracil (PTU) inhibit thyroid
peroxidase-catalyzed synthesis of thyroid hormones,
and thereby help in maintaining a euthyroid state in
patients with Graves disease. Although ATD therapy
is not causal, 20%50% of patients with Graves disease enter remission after its initiation, depending on
the duration of follow-up [1-3]. ATDs should be discontinued when the patient is expected to enter remission. However, no standard protocol exists to determine the timing of ATD cessation. In Europe and
the United States [4-6], in patients with Graves disReceived Sep. 6, 2010; Accepted Dec. 10, 2010 as K10E-262
Released online in J-STAGE as advance publication Dec. 28, 2010
Konishi et al.
Results
Outcomes
In total 18 of 107 patients exhibited transient thyrotoxicosis 320 months (median 9.0 months) after ATD
withdrawal. When these 18 patients were regarded as
remission cases, the percentage of patients with remission was 86.9% (93/107) at 6 months, 73.8% (79/107) at
1 year, and 68.2% (73/107) at 2 years after discontinuation of ATD therapy. Thirty-four patients relapsed within
2 years after ATD discontinuation. Of these 34 patients,
14 (41.1%) relapsed within the first 6 months and 28
(82.4%) relapsed within 1 year of ATD discontinuation.
Table 1 Comparisons of the duration of antithyroid drug (ATD) therapy, period from the start of ATD
therapy to the beginning of minimum maintenance dose (MMD), duration of ATD therapy with
MMD in patients in whom hyperthyroidism relapsed during 2 years after cessation of ATD (relapse
group), and that in patients who were euthyroid 2 years after cessation of ATD (remission group).
Relapse group
(n = 34)
Remission group
(n = 73)
54.4 45.3
44.8 44.8
Period from the start of ATD therapy to the beginning of MMD (months)
47.3 43.4
34.6 42.9*
7.1 3.9
10.2 7.1*
Values are means SD. Differences were evaluated by the Mann-Whitney U-test.
*P < 0.05 for relapse group vs. remission group
*P< 0.05
100
90
80
Remission rate (%)
70
60
50
40
30
20
10
0
Fig. 1
6
n = 49
712
1318
38
7
MMDT Period (months)
19
13
more) were 63.2%, 65.8%, 71.4%, and 92.3%, respectively. Remission rates increased as the MMDT duration increased, and the remission rate in patients with
19 months or more of MMDT was significantly higher
than that in patients with 6 months or less of MMDT
(92.3% vs. 63.2%; P < 0.05). There were no differences
in serum concentrations of FT3, FT4, and TRAb and
the thyroid volume at the start of ATD therapy among
patients irrespective of MMDT duration (Table 2).
Konishi et al.
Table 2 Comparison of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) receptor
antibody (TRAb) levels and thyroid volume at the start of ATD therapy in patients with minimum maintenance
dose therapy (MMDT) durations of 6 months or less, 7 to 12 months, 13 to 18 months, and 19 months or more.
MMDT duration (months)
6
712
1218
19
FT3 (pg/mL)
17.8 6.9
16.5 7.3
17.0 8.1
18.2 8.0
FT4 (ng/dL)
5.4 2.1
5.2 2.0
5.3 2.5
5.4 2.2
TRAb (U/L)
14.2 17.9
14.5 19.5
16.8 16.0
13.0 13.7
27.4 13.5
24.9 9.8
24.2 8.5
25.8 11.3
Discussion
100
TRAb positive
TRAb negative
80
70
60
50
40
30
20
10
0
*P< 0.05
90
n=
6
23 26
711
15 19
MMDT Period (months)
12
4 20
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