Antithyroid Drugs and Graves' Disease: A Prospective Randomized Evaluation of the Efficacy of Treatment Duration

Allannic, H; Fauchet, R.; Orgiazzi, Jacques; Orgiazzi, A. M.; Genetet, B; Lorcy, Y.; Guerrier, A. M. Le; Delambre, C.; Derennes, V.

doi:10.1210/jcem-70-3-675

Cited by 167 publications

(103 citation statements)

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“…Suppression of thyrotropin (TSH) stimulation of the thyroid gland by adding exogenous L-thyroxine (L-T 4 ) to ATD treatment may be beneficial (6,7), and direct immunomodulatory effects of high doses of ATD or L-T 4 have also been proposed (1,8). In clinical studies, however, the relapse rates of Graves' disease have varied from 2 to 60% (8,9), and the impact of different treatment regimens and predictors of outcome, such as TRAb and smoking, remains a matter of controversy (3,(10)(11)(12)(13). It is therefore of clinical interest to identify treatment regimens that lower relapse rates.…”

Section: Introductionmentioning

confidence: 99%

Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves' disease

Nedrebø¹,

Holm²,

Uhlving³

et al. 2002

European Journal of Endocrinology

119

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Objective: To investigate the effect of different antithyroid drug (ATD) regimens on relapse rates of Graves' disease, and to look for predictors of relapse. Design and Methods: In a prospective two-way factorial randomized clinical trial, 218 patients with Graves' disease were assigned to ATD combined with L-thyroxine (L-T 4 ) or ATD alone for 12 months. After discontinuation of antithyroid therapy, each group was stratified to either 12 months further treatment with L-T 4 or no treatment. Clinical and biochemical assessments were carried out before treatment, after 3 and 6 weeks, and every third month for 12 months. If the patients lacked symptoms of relapse, laboratory tests were performed every third month for the second year, and thereafter annually. Results: The proportion of all patients with relapse was 47.7% 2 years after withdrawal of ATD. There was no difference in relapse rates between the treatment groups (P ¼ 0:217; log-rank test). Smokers had a higher relapse rate than non-smokers (58.4% vs 38.8%, P ¼ 0:009). Patients who were thyrotropin-receptor antibody (TRAb) positive after 12 months of antithyroid therapy had a higher relapse rate than those who were negative (72.5% vs 36.8%, P , 0:0001). Similarly, relapse was more frequent (55.5%) in patients having large goiter compared with subjects with small goiter (36.3%, P ¼ 0:0007). Conclusions: Relapse rates of Graves' disease were independent of ATD regimen whether followed by L-T 4 therapy or not. Smoking, large goiter and presence of TRAb at the end of ATD therapy were strong predictors of relapse.

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Section: Introductionmentioning

confidence: 99%

Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves' disease

Nedrebø¹,

Holm²,

Uhlving³

et al. 2002

European Journal of Endocrinology

119

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“…Very few of these studies previously published on anti-pancreatic immunity in Caucasian endocrine patients, were homogeneous with regard to the initial disease and the intensity of extra-pancreatic autoimmunity at the time of sampling and studied the whole range of humoral markers available. In our clinic of endocrine diseases, we have a large recruitment of patients at diagnosis of Graves' disease (GD) (17)(18)(19)(20) and most anti-pancreatic markers (ICA, IAA, GAD/ 64 kDa, 37/40 kDa autoantibodies) are available in our laboratory. The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed GD in order to characterize the specific features of this group of endocrine patients among subjects at risk of diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…GD diagnosis was based upon the usual clinical and biological signs including determination of free thyroid hormones and thyroid stimulating hormone, as well as scintigraphic criteria (homogeneous thyroid scans). All patients received carbimazole for 6-36 months according to various protocols (17)(18)(19)(20). The sera were collected upon diagnosis, before initiation of any specific treatment.…”

Section: Introductionmentioning

confidence: 99%

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

Maugendre¹,

Verite²,

Guilhem³

et al. 1997

European Journal of Endocrinology

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The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed Graves' disease (GD), in order to characterize the specific features of this group of endocrine patients among subjects at risk of diabetes.Ten were already diabetic at GD diagnosis. Among the 590 non-diabetic patients, 29 had islet cell antibodies (ICA), including 15 with low titre ICA and only 1 ICA-positive subject with a familial history of diabetes. Twenty-four patients had insulin autoantibodies, including three in association with ICA. Glutamic acid decarboxylase (GAD)/64 kDa antibodies were found in 16 of the 150 tested sera, including 13 of the 29 ICA-positive sera. Four ICA-positive patients displayed 37/40 kDa antibodies, including three in association with GAD/64 kDa antibodies. During follow-up, one of the ICA-positive patients developed insulin-dependent diabetes, 14 years after the GD diagnosis.To summarize, this anti-pancreatic autoimmunity study was focused on a large but specific and homogeneous group of subjects at risk for diabetes: recently diagnosed GD patients. This population was characterized by a high prevalence of GAD/64 kDa antibodies but also by a low frequency of evolution towards diabetes and the slowness of the process which could be due to the fact that only a minority of subjects possessed a sufficient combination of anti-pancreatic markers at the same time.

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“…In one study (4,5) the longer-duration Titration regimen (18 months) had significantly fewer relapses than the 6 month group (RR ¼ 0.63, 95% CI 0.41 to 0.99). One study (6) found there was no significant difference between 12 and 6 months (RR ¼ 0.86, 95% CI 0.52 to 1.43) using the Block-Replace regimen.…”

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confidence: 99%

A systematic review of drug therapy for Graves’ hyperthyroidism

Abraham

Avenell

Park³

et al. 2005

eur j endocrinol

178

113

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We assessed the effects of dose, regimen and duration of anti-thyroid drug therapy for Graves' thyrotoxicosis on recurrence of hyperthyroidism, course of ophthalmopathy, adverse effects, health-related quality of life and economic outcomes. We undertook a systematic review and meta-analyses of randomised controlled trials (RCTs). We identified RCTs regardless of language or publication status by searching six databases, and trial registries. Dual, blinded data abstraction and quality assessment were undertaken. Trials included provided therapy for at least 6 months with follow-up at least 1 year after drug cessation. Fixed or random effects meta-analyses were used to combine study data. Twelve trials compared a Block-Replace regimen (requiring a higher dose of anti-thyroid drug treatment) with a Titration regimen. Overall, there was no significant difference between the regimens for relapse of hyperthyroidism (relative risk (RR) ¼ 0.93, 95% confidence interval (CI) 0.84 to 1.03). Participants were more likely to withdraw due to adverse events with a Block-Replace regimen (RR ¼ 1.89, 95% CI 1.25 to 2.85). Prescribing replacement thyroxine, either with the anti-thyroid drug treatment, or after this was completed, had no significant effect on relapse. Limited evidence suggested 12-18 months of anti-thyroid drug treatment should be used. The titration regimen appeared as effective as the Block-Replace regimen, and was associated with fewer adverse effects. However, relapse rates over 50% and high participant drop-out rates in trials mean that the results should be interpreted with caution, and may suggest that other strategies for the management of Graves' disease, such as radioiodine, should be considered more frequently as first-line therapy. There were no data on the course of ophthalmopathy, health-related quality of life and economic outcomes.European Journal of Endocrinology 153 489-498

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Antithyroid Drugs and Graves' Disease: A Prospective Randomized Evaluation of the Efficacy of Treatment Duration

Cited by 167 publications

References 0 publications

Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves' disease

Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves' disease

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

A systematic review of drug therapy for Graves’ hyperthyroidism

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