To Örebro University

BACKGROUND: The treatment efficacy of antithyroid drug therapy (ATD), radioactive iodine (I131) or surgery for Graves' hyperthyroidism is well described. However, there are few reports on the long-term total outcome of each treatment modality as how many require levothyroxine supplementation, the need of thyroid ablation or the individual patient's estimation of their recovery.

METHODS: We conducted a pragmatic trial to determine the effectiveness and adverse outcome in a patient cohort newly diagnosed with Graves' hyperthyroidism between 2003-2005 (n=2430). The patients were invited to participate in a longitudinal study spanning 8±0.9years (mean±SD) after diagnosis. We were able to follow 1186 (60%) patients that had been treated with ATD, I131 or surgery. We determined the mode of treatment, remission rate, recurrence, quality of life, demographic data, comorbidities and lifestyle factors through questionnaires and review of the individual medical history records.

RESULTS: At follow-up the remission rate after first line treatment choice with ATD was 45.3% (351/774), with I-131 therapy 81.5% (324/264) and with surgery 96.3% (52/54). Among those patients who had a second course of ATD 29.4% achieved remission. The total number of patients who had undergone ablative treatment was 64.3% (763/1186), of which 23% (278/1186) had received surgery, 43% (505/1186) I-131 therapy including 2% (20/1186) who received both surgery and I-131. Patients who received ATD as first treatment and possibly additional ATD had 49.7% risk (385/774) of having undergone ablative treatment at follow-up. Levothyroxine replacement was needed in 23% (81/351) of the initially ATD treated in remission, in 77.3% (204/264) of the I131treated and in 96.2% (50/52) of the surgically treated patients. Taken together after 6-10 years, and all treatment considered, normal thyroid hormone status without thyroxine supplementation was only achieved in 35.7% (423/1186) of all patients and in only 40.3% of those initially treated with ATD. The proportion of patients that did not feel fully recovered at follow-up was 25.3%.

CONCLUSION: A patient selecting ATD therapy as the initial approach in the treatment of Graves' hyperthyroidism should be informed that they have only a 50.3% chance of ultimately avoiding ablative treatment and only a 40% chance of eventually being euthyroid without thyroid medication. Surprisingly, 1 in 4 patients did not feel fully recovered after 6-10 years. The treatment for Graves' hyperthyroidism, thus has unexpected long-term consequences for many patients.

BACKGROUND: Hyperthyroidism is known to have a significant impact on the quality of life (QoL) at least in the short term. The purpose of the present study was to assess QoL in patients at 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both a thyroid-specific (ThyPRO) and general (SF-36) QoL surveys.

METHODS: We evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 which had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n=975) and/or the SF-36 questionnaire (n=964) and informed consent at follow-up. Scores from ThyPRO were compared with scores from a general population sample (n=712), using multiple linear regression adjusting for age and gender as well as multiple testing. Treatment related QoL outcome for ATD, RAI and surgery were compared including adjustment for the number of treatments received, sex, age and co-morbidity.

RESULTS: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared with the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL-scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism.

CONCLUSIONS: Graves' disease is associated with a lower QoL many years after treatment compared to the general population. In a previous, small RCT we did not show any difference in patient satisfaction years after ATD, RAI or surgery. We now report that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and SF-36. These findings in a Swedish population are limited by comparison to normative data from Denmark, by older age and possibly a more prolonged course in those patients who received radioiodine, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown but since the results may be important for future considerations regarding treatment options for GD they need to be substantiated in further studies.