To Örebro University

BACKGROUND: The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort.

METHODS: TNG patients (n = 638) de novo diagnosed between 2003-2005 were invited to engage in a 6-10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines.

RESULTS: The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population.

CONCLUSION: One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG.

Introduction: The treatment strategies for a 42-year-old female index patient with moderate Graves' disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed.

Materials and Methods: From a Swedish cohort of 1186 GD patients (TT-12 cohort), 27 women were identified using the same criteria as from the index patient surveys from the European and American Thyroid Associations. This 'index patient cohort' was age 40-45, otherwise healthy female, with two children and uncomplicated GD. The applied first-line treatment of the patients in the index cohort, together with its variations, was compared with the treatment preferences according to international surveys. A comparison with the TT-12 cohort was also performed.

Results: In the 'Index cohort', 77.8% were treated with antithyroid drugs (ATD), and 22.2% were treated with radioiodine (¹³¹I). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where ¹³¹I was preferred. The distribution of treatment in the TT-12 cohort did not significantly differ from the index cohort. ATD was the preferred treatment in male and young (age 19-22) patients, as was RAI in old (age 69-73) patients. The age-related, but not the gender-related, cases differed significantly from the entire TT-12 cohort.

Conclusion: The treatment choice in an index patient in Sweden seems in line with European practice, where ATD is the preferred first choice. This differs compared to US and North African survey intentions, where ¹³¹I is more often used. Age more than gender influences the treatment choice of GD patients. This is, to our best knowledge, the first time an index patient from 'real life' has been presented and compared to treatment preferences of international thyroid association surveys.

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.

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.

Treatment of Graves’ disease (GD) and toxic nodular goiter (TNG) has the objectives to cure hyperthyroidism, prevent recurrent disease and preserve thyroid function. Treatment efficacies and long-termout comes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery varies in the literature. We report outcome of treatment, cure rate and risk factors for relapse for GD and TNG in an unselected cohort. A prospective incidence-cohort of de novo diagnosed GD and TNG patients (n = 2916) from 2003-05, were invited to a follow-up 6 - 10 years after diagnosis. Questionnaires were sent to 2430 patients regarding treatments, cure rate, recurrence, quality of life, demographic data, comorbidities and life-style factors. Patients were treated according to clinical routine with ATD, RAI or surgery. Of those included, 1186 (83.3%) had GD and 237 (16.7%) had TNG. In GD patients, 351 (45.3%), 264 (81.5%), and 52 (96.3%) were cured by ATD, RAI or surgery respectively as first line treatment. Of those, 77.0%, 15.4% and 3.8% respectively were without levothyr-oxine supplementation at follow-up at 8 – 0.9 years. Including all treatment modalities, 851 (71.8%) of GD patients were cured within one treatment period. At follow-up, 278 (23%) of GD patients had been operated. In TNG patients, RAI cured 88.6% and surgery 92.9%, whereof 52/154 (33.8%) and 3/15 (20%) had no levothyroxine supplementation post RAI and surgery, respectively.The proportion that did not feel fully recovered at follow-up was 25.3% of GD and 18.1% of the TNG patients. Overall, treatment of hyperthyroidism results in preserved thyroid function only in 35.3% and 44.7% of GD and TNG cases, respectively. As many as 23.4% of the GD patients end up with surgery although only 4.6% choose it from the beginning. Our treatment tradition cures 71.8% of GD patients and 78.1% of TNG patients within one treatment period. The high number of patients who do not feel recovered 6 -10 years after hyperthyroidism in GD and TNG is are minder of the chronic nature of hyperthyroidism.

Introduction: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100000 inhabitants per year. This extended study has evaluated the incidence for similar to 40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. Methods:All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows:clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. Results:A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. Conclusion:The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.