Endocrine Journal 2009, 57

Original

Advance Publication
doi: 10.1507/endocrj. K10E-262

Drug discontinuation after treatment with minimum

maintenance dose of an antithyroid drug in Graves disease:
a retrospective study on effects of treatment duration with
minimum maintenance dose on lasting remission
Toshiaki Konishi1), Yasuyuki Okamoto2), Miki Ueda1), Yoshiko Fukuda2), Ichiko Harusato1),
Yuka Tsukamoto2) and Noboru Hamada1)
1)
2)

Sumire Hospital, Osaka 536-0001, Japan

Sumire Clinic, Osaka 535-0071, Japan

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

Correspondence to: Toshiaki Konishi M.D., Sumire Hospital,

Osaka Social Welfare Foundation, 1-20-85, Furuichi, Joto-ku,
Osaka 536-0001, Japan. E-mail: konishi@sumire-hosp.com
The Japan Endocrine Society

ease, ATDs are discontinued after a fixed period (12

years) of treatment, because the remission rate does not
increase statistically after 18 months of treatment [7-9].
The timing of ATD cessation is difficult to determine
because there are no measures for accurately evaluating the activity of Graves disease. For this purpose,
the triiodothyronine (T3) suppression test [10, 11], thyroid releasing hormone test [12, 13], T3/thyroxine (T4)
ratio [14] and serum thyroglobulin [15, 16] and thyroid
stimulating hormone (TSH) receptor antibody (TRAb)
[2, 3, 17-24] levels have been used, but acceptable
results have not been obtained.
The criterion for ATD discontinuation was proposed by the Japan Thyroid Association in its guideline for the treatment of Graves disease [25]. In this
guideline, ATD discontinuation is recommended when
serum free thyroxine (FT4) and TSH concentrations

Konishi et al.

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). This guideline is based on the observation
that remission rates after ATD withdrawal are higher
(63.4%80%) in patients for whom ATD therapy was
stopped after the euthyroid state was maintained for
36 months with MMDT [26-28] than that (42%51%)
in patients for whom ATD was stopped regardless of
the ATD dosage after 2 years of ATD therapy [14, 29].
The guideline suggests that the duration of MMDT
should be 6 months or more; however, there is no
evidence to validate the viability of this duration.
Therefore, in the present study, we investigated the
optimal MMDT duration for a patient to be in remission after discontinuation of ATD.

Subjects and Method

Patients
The participants were 107 consecutive patients with
Graves disease (92 females, 15 males; median age, 36
years; range, 1574 years) for whom ATD therapy was
stopped according to the guideline issued by the Japan
Thyroid Association [25] between February 2002
and September 2007 in our hospital. Graves disease
was diagnosed in the clinical and laboratory findings,
including signs of thyrotoxicosis, diffuse goiter, eye
signs, elevation of serum FT4 and free T3 (FT3) concentrations, suppression of serum TSH concentrations,
TRAb positivity, and elevated radioiodine uptake for
24 h when it was necessary. The patients were treated
with ATDs, and the dose of ATDs was titrated to maintain patients in the euthyroid state. When serum FT4
and TSH concentrations were within the reference
range for 6 months or more with 5 mg/day of MMI
or 50 mg/day of PTU, the dose of MMI or PTU was
further decreased to 5 mg every other day or 50 mg
every other day (minimum maintenance dose, MMD),
respectively. When serum FT4 and TSH concentrations were within the reference range following treatment with MMDT for 3 months or more, ATD was
discontinued after obtaining informed consent. The
therapeutic period of ATDs was 48 45 months (mean
SD; range 7273 months).
Serum FT4, TSH, and TRAb levels were measured
at the time of ATD discontinuation and every 3 months
thereafter. Patients were considered to have relapsed
when their serum TSH levels decreased persistently

to less than the reference range. Patients who once

exhibited a decrease in serum TSH concentrations after
ATD discontinuation but showed normalization of their
serum TSH concentrations thereafter without restarting
ATD were defined as cases of transient thyrotoxicosis.
Patients who maintained a euthyroid state after discontinuation of ATDs and patients in whom thyroid function was maintained in a euthyroid state after transient
thyrotoxicosis were regarded as remission cases. The
patients were followed up for at least 2 years after ATD
withdrawal. This study was approved by the ethical
committee of Sumire Hospital, and informed consent
was obtained from all patients.
Measurements
The serum concentrations of TSH (reference range:
0.384.31 IU/mL), FT3 (reference range: 2.13.8
pg/mL), and FT4 (reference range: 0.821.63 ng/dL)
were measured by enzyme immunoassay using commercially available kits (TSH: ST AIA-PACK TSH,
FT3: ST AIA-PACK FT3, FT4: ST AIA-PACK FT4;
Tosoh Corporation, Tokyo, Japan). Serum TRAb levels were measured by the DYNO test TRAb human kit
from Yamasa Corporation (Tokyo, Japan). The TRAb
results are expressed in U/L of international reference
preparation NIBSC 90/672, and values below 1.0 U/L
were considered negative, as recommended by the kits
manufacturer.
Statistical analysis
The non-parametric Mann-Whitney U-test was used
for comparing the means of two groups. Frequencies
were compared using the 2 test with Fishers correction, when appropriate. P-values < 0.05 were considered statistically significant.

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.

Endocrine Journal Advance Publication

ATD therapy in Graves disease

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)

Duration of ATD therapy (months)

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*

Duration of ATD therapy with MMD (months)

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 (%)

Relationship between ATD therapeutic period and

outcome
ATD therapeutic periods were compared between
patients in remission (remission group) and patients
in whom Graves hyperthyroidism relapsed during
the 2-year period after the cessation of ATD therapy
(relapse group; Table 1). There were no differences in
the serum concentrations of FT3 and FT4 and the thyroid volume at the start of ATD therapy between the
remission and relapse groups (FT3: 17.5 7.2 vs. 17.1
7.4 pg/mL, FT4: 5.4 2.1 vs. 5.20 2.1 ng/dL, thyroid volume: 25.4 12.1 vs. 27.6 10.8 g). TRAb
levels at the time of ATD withdrawal in the relapse
group were significantly higher than that in the remission group (1.1 1.8 U/L vs. 0.6 1.1 U/L; P < 0.05).
The period from the start of ATD therapy to the beginning of MMDT was significantly shorter in the remission group than in the relapse group. Remission rates
in each group divided according to the period (less than
1 year, from 1 year to less than 2 years, from 2 years to
less than 3 years, and 3 years or more) from the start of
ATD therapy to the beginning of MMDT were 81.5%,
69.6%, 64.7%, and 60%, respectively. The remission
rate tended to be higher if the period from the start of
ATD to the beginning of MMDT was shorter, although
the difference was not significant. The total ATD therapeutic period tended to be shorter in the remission
group than in the relapse group, but the difference was
not significant.
The relationship between MMDT durations and the
remission rate is shown in Fig. 1. Remission rates in
each group divided according to the duration of ATD
therapy with MMDT (6 months or less, from 7 to
12 months, from 13 to 18 months, and 19 months or

70
60
50
40
30
20
10
0

Fig. 1

6
n = 49

712
1318
38
7
MMDT Period (months)

19
13

Relationship between remission rates estimated 2 years

after the cessation of antithyroid drug (ATD) treatment
and the duration of minimum maintenance dose therapy
(MMDT) in patients with Graves disease.

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).

Endocrine Journal Advance Publication

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

Thyroid volume (g)

27.4 13.5

24.9 9.8

24.2 8.5

25.8 11.3

Values are means SD. Not significant among groups.

Discussion

100

TRAb positive
TRAb negative

80
70
60
50
40
30
20
10
0

As reported earlier [26-28], the remission rate in this

study in which ATD therapy was stopped according to
the guideline issued by the Japan Thyroid Association
was higher than that in studies of conventional ATD
therapy, in which ATD was stopped regardless of the
ATD dose after a fixed period of treatment in patients
with Graves disease [1-3, 14, 29]. The activity of
Graves disease appeared to be low in patients whose
serum FT4 and TSH concentrations were maintained
for a long time within the reference range with MMDT.
Therefore, the high remission rate observed in this
study is believed to be because of the fact that patients
with low Graves disease activity were selected and not
because of the treatment method.
The high remission rate in a study in which ATD
was discontinued after a certain MMDT duration was
observed [25]. However, the duration of treatment in
the study was longer than that of conventional ATD therapy. In fact, the duration of ATD therapy was approximately 4 years (median) in the study by Okamoto et al.
[27] and was 73.5 months (mean value) for the remission group and 60.3 months for the relapse group in a

*P< 0.05

90

Remission rate (%)

Comparison of remission rates between TRAb-positive

and -negative patients measured at the time of ATD
withdrawal, in relation to MMDT durations (Fig. 2)
In patients with MMDT durations of 6 months or
less, the remission rate in TRAb-positive patients at the
time of ATD withdrawal was significantly lower than
that in TRAb-negative patients (47.8% vs. 76.9%; P <
0.05) (Fig. 2). However, the difference in remission
rates between TRAb-positive and -negative patients
disappeared in patients with MMDT durations of 7
months or more.

n=

6
23 26

711
15 19
MMDT Period (months)

12
4 20

Fig. 2 Comparison of the remission rate between patients with

TRAb-positive and -negative measured at the time of
withdrawal of ATD in relation to the duration of MMDT.

study by Kashiwai et al. [28]. However, in this study,

the total ATD therapy duration tended to be shorter in
the remission group than in the relapse group, although
the difference was not significant. Furthermore, the
period from the start of ATD therapy to the beginning
of MMDT was significantly shorter in the remission
group than in the relapse group. These results are consistent in patients whose TRAb levels decreased in the
early stages of Graves disease treatment with ATD
therapy and in those who could easily achieve remission [19-22]. The high remission rate observed with
MMDT was not because of the longer duration of ATD
therapy. Therefore, it is suggested that when treating
Graves disease using ATD therapy, the ATD dose can

Endocrine Journal Advance Publication

ATD therapy in Graves disease

be decreased when serum FT4 and TSH concentrations

were within the reference range for a certain period
of time. If serum FT4 and TSH concentrations were
maintained within the reference range with MMDT for
3 months or more, ATD could be discontinued regardless of the ATD therapy duration.
We investigated the appropriate MMDT duration for
patients in remission after discontinuation of ATD. In
this study, the remission rate increased with the MMDT
duration, 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.
Although this study was retrospective, there were no differences in FT3, FT4, and TRAb serum concentrations
and thyroid volume at the start of ATD therapy among
the groups of patients divided by MMDT duration. The
following two possibilities were considered for the longer durations of MMDT being associated with higher
remission rates. (1) Patients with low Graves disease
activity were selected during long duration of MMDT
by drop-out of the patients with high Graves disease
activity. (2) Remission was associated with long duration of euthyroid state, as Laurbergs hypothesis on the
mechanism of Graves disease remission during ATD
therapy [30], that is, remission is associated with restoration of the euthyroid state.

TRAb measurements are a predictor of outcome for

ATD therapy for Graves disease because of its pathogenic role. Patients whose TRAb values do not decrease
in the early stages of Graves disease treatment with
ATD do not achieve remission [19-22]. Furthermore,
the relapse rate is higher in TRAb-positive patients
than in TRAb-negative patients at the time of ATD
withdrawal [21, 23, 27]. In this study, in patients with
MMDT durations of 6 months or less, the remission
rate in patients with TRAb positivity at the time of ATD
withdrawal was significantly lower than that in patients
with TRAb negativity. However, the difference in
remission rates between TRAb-positive and -negative
patients disappeared in those with MMDT durations of
7 months or more. TRAb does not always stimulate
the thyroid gland because TRAb is an expression of
the binding activity of IgG to the TSH receptor. Serum
TRAb levels measured in patients being maintained in
a euthyroid state for an extended MMDT duration may
be too low to stimulate thyroid gland activity.
In conclusion, the remission rate increases as the
MMDT duration increases in patients who discontinue
ATD after a certain MMDT duration, and ATD should
not be discontinued in TRAb-positive patients with
MMDT durations of 6 months or less.

References
1. Hedley AJ, Young RE, Jones SJ, Alexander WD,
Bewsher PD (1989) Antithyroid drugs in the treatment
of hyperthyroidism of Graves disease: long-term follow-up of 434 patients. Scottish Automated Follow-Up
Register Group. Clin Endocrinol (Oxf). 31: 209-218.
2. Schleusener H, Schwander J, Fischer C, Holle R, Holl
G, Badenhoop K, Hensen J, Finke R, Bogner U, Mayr
WR et al (1989) Prospective multicentre study on the
prediction of relapse after antithyroid drug treatment in
patients with Graves disease. Acta Endocrinol (Copenh)
120: 689-701.
3. Vitti P, Rago T, Chiovato L, Pallini S, Santini F, Fiore
E, Rocchi R, Martino E, Pinchera A (1997) Clinical features of patients with Graves disease undergoing remission after antithyroid drug treatment. Thyroid 7: 369375.
4. Singer PA, Cooper DS, Levy EG, Ladenson PW,
Braverman LE, Daniels G, Greenspan FS, McDougall
IR, Nikolai TF (1995) Treatment guidelines for patients
with hyperthyroidism and hypothyroidism. Standards of
Care Committee, American Thyroid Association. JAMA

273: 808-812.
5. Vanderpump MP, Ahlquist JA, Franklyn JA, Clayton
RN (1996) Consensus statement for good practice and
audit measures in the management of hypothyroidism
and hyperthyroidism. The Research Unit of the Royal
College of Physicians of London, the Endocrinology and
Diabetes Committee of the Royal College of Physicians
of London, and the Society for Endocrinology. BMJ
313: 539-544.
6. Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler
RB, Kaplan MM, Segal RL; American Association of
Clinical Endocrinologists. (2002) American Association
of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 8: 457469.
7. Maugendre D, Gatel A, Campion L, Massart C, Guilhem
I, Lorcy Y, Lescouarch J, Herry JY, Allannic H (1999)
Antithyroid drugs and Graves disease--prospective
randomized assessment of long-term treatment. Clin
Endocrinol (Oxf) 50: 127-132.

Endocrine Journal Advance Publication

Konishi et al.

8. Wartofsky L, Glinoer D, Solomon B, Nagataki S,

Lagasse R, Nagayama Y, Izumi M. (1991) Differences
and similarities in the diagnosis and treatment of Graves
disease in Europe, Japan, and the United States. Thyroid
1: 129-135.
9. Glinoer D, Hesch D, Lagasse R, Laurberg P (1987) The
management of hyperthyroidism due to Graves disease
in Europe in 1986. Results of an international survey.
Acta Endocrinol (Copenh) 285 (Suppl): 3-23.
10. Yamamoto M, Totsuka Y, Kojima I, Yamashita N,
Togawa K, Sawaki N, Ogata E (1983) Outcome of
patients with Graves disease after long-term medical
treatment guided by triiodothyronineT3suppression test. Clin Endocrinol (Oxf) 19: 467-476.
11. Takasu N, Akamine H, Komiya I, Yamada T (1995)
Simple and reliable method for predicting the remission of Graves disease: revised triiodothyronine-suppression test, indexed by serum thyroxine. J Endocrinol
Invest. 18: 288-294.
12. Dahlberg PA, Karlsson FA, Jansson R, Wide L (1985)
Thyrotropin-releasing hormone testing during antithyroid drug treatment of Graves disease as an indicator of
remission. J Clin Endocrinol Metab 61: 1100-1104.
13. Notsu K, Oka N, Masaki Y, Furuya H, Kato Y (1991)
Plasma tree triiodothyronine response to thyrotropin-releasing hormone to predict the remission of Graves disease treated with antithyroid drugs. J Clin Endocrinol
Metab 73: 396-400.
14. Takamatsu J, Kuma K, Mozai T (1986) Serum triiodothyronine to thyroxine ratio: A newly recognized
predictor of the outcome of hyperthyroidism due to
Graves disease. J Clin Endocrinol Metab 62: 980-983.
15. Kawamura S, Kishino B, Tajima K, Mashita K, Tarui
S (1983) Serum thyroglobulin changes in patients with
Graves disease treated with long term antithyroid drug
therapy. J Clin Endocrinol Metab 56: 507-512.
16. Talbot JN, Duron F, Feron R, Aubert P, Milhaud G
(1989) Thyroglobulin, thyrotropin and thyrotropin
binding inhibiting immunoglobulins assayed at the
withdrawal of antithyroid drug therapy as predictors of
relapse of Graves disease within one year. J Endocrinol
Invest 12: 589-595
17. Chowdhury TA, Dyer PH (1998) Clinical, biochemical and immunological characteristics of relapsers and
non-relapsers of thyrotoxicosis treated with anti-thyroid
drugs. J Intern Med 244: 293-297.
18. Winsa B, Dahlberg A, Jansson R, Agren H, Karlsson
FA (1990) Factors influencing the outcome of thyrostatic drug therapy in Graves disease. Acta Endocrinol
(Copenh) 122: 722-728.
19. Michelangeli V, Poon C, Taft J, Newnham H, Topliss
D, Colman P (1998) The prognostic value of thyrotropin receptor antibody measurement in the early stages

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

of treatment of Graves disease with antithyroid drugs.

Thyroid 8: 119-124.
Takasu N, Yamashiro K, Komiya I, Ochi Y, Sato Y,
Nagata A (2000) Remission of Graves hyperthyroidism predicted by smooth decreases of thyroid-stimulating antibody and thyrotropin-binding inhibitor immunoglobulin during antithyroid drug treatment. Thyroid
10: 891-896.
Schott M, Morgenthaler NG, Fritzen R, Feldkamp
J, Willenberg HS, Scherbaum WA, Seissler J (2004)
Levels of autoantibodies against human TSH receptor
predict relapse of hyperthyroidism in Graves disease.
Horm Metab Res 36: 92-96.
Cappelli C, Gandossi E, Castellano M, Pizzocaro C,
Agosti B, Delbarba A, Pirola I, De Martino E, Rosei EA
(2007) Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves disease: a 120 months prospective study. Endocr J 54: 713-720.
Feldt-Rasmussen U, Schleusener H, Carayon P (1994)
Meta-analysis evaluation of the impact of thyrotropin
receptor antibodies on long term remission after medical therapy of Graves disease. J Clin Endocrinol Metab
78: 98-102.
Kawai K, Tamai H, Matsubayashi S, Mukuta T, Morita
T, Kubo C, Kuma K (1995) A study of untreated Graves
patients with undetectable TSH binding inhibitor immunoglobulins and the effect of anti-thyroid drugs. Clin
Endocrinol (Oxf) 43: 551-556.
Guideline for the treatment of Graves disease with antithyrid drug in Japan. The Japan Thyroid Association,
2006, Nankodo Co., Ltd., Tokyo.
Tajiri J, Noguchi S, Morita M, Tamaru M, Murakami N
(1991) Antithyroid drug therapy for Graves hyperthyroidism: is long-term administration of a small maintenance dose necessary? Endocrinol Jpn 38: 223-227.
Okamoto Y, Tanigawa S, Ishikawa K, Hamada N (2006)
TSH receptor antibody measurements and prediction of
remission in Graves disease patients treated with minimum maintenance doses of antithyroid drugs. Endocr J
53: 467-472.
Kashiwai T, Hidaka Y, Takano T, Tatsumi KI, Izumi
Y, Shimaoka Y, Tada H, Takeoka K, Amino N (2003)
Practical treatment with minimum maintenance dose of
anti-thyroid drugs for prediction of remission in Graves
disease. Endocr J 50: 45-49.
Mashio Y, Beniko M, Matsuda A, Koizumi S, Matsuya
K, Mizumoto H, Ikota A, Kunita H (1997) Treatment
of hyperthyroidism with a small single daily dose of
methimazole: a prospective long-term follow-up study.
Endocr J 44: 553-558.
Laurberg P (2006) Remission of Graves disease during
anti-thyroid drug therapy. Time to reconsider the mechanism? Eur J Endocrinol 155: 783-786.

Endocrine Journal Advance Publication