Introduction: Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism. Objective: To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSHreceptor autoimmunity. Methods: Patients with newly diagnosed Graves' hyperthyroidism aged 20-55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients R35 years of age). L-thyroxine (L-T 4 ) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy. Results: Medical therapy (nZ48) and surgery (nZ47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70-80% of the patients after 18 months. Radioiodine therapy (nZ36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy. Conclusion: The majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.

Radioiodine treatment is a significant risk factor for development of TAO in Graves' hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.

Introduction: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100 000 inhabitants per year. This extended study has evaluated the incidence for w40% 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][2004][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 (TNGZSTACTMNG) 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.

BACKGROUND: Despite low anterior resection syndrome being a well-known consequence of sphincter-preserving rectal cancer surgery, the long-term effect on bowel function and quality of life is not fully understood. OBJECTIVE: This study aimed to elucidate whether symptoms of low anterior resection syndrome change over time and if the correlation to quality of life is equivalent when measured at 2 time points. DESIGN: This prospective cohort study included measurements at 2 time points (5 years between; range, 7.1–16.1 years from surgery to second follow-up). SETTINGS: This multicenter study included patients from Sweden and Denmark. PATIENTS: Patients were included if they were ≥18 years of age and underwent curative rectal cancer surgery with either total or partial mesorectal excision. MAIN OUTCOME MEASURES: Outcomes were measured with the low anterior resection syndrome questionnaire including a question assessing the impact of bowel function on quality of life and with the validated quality-of-life questionnaire EORTC QLQ-C30. RESULTS: In total, 282 patients were included and there were no statistically significant differences in the distribution among the 3 groups (no, minor, and major low anterior resection syndrome) when comparing time points follow-up 1 with follow-up 2 (p = 0.455). At follow-up 2, 138 patients (49%) still experienced major impairment. No both statistically and clinically significant differences were seen in the mean score of EORTC QLQ-C30 when comparing the same low anterior resection syndrome group at follow-up 1 and follow-up 2, and the impact on quality of life was comparable. Global health status/quality of life was impaired in the major low anterior resection syndrome group at both follow-up 1 (p < 0.001) and follow-up 2 (p < 0.001). LIMITATIONS: The study design prevents an evaluation of causality. CONCLUSIONS: Difficulties with low anterior resection syndrome and the impact on patients’ quality of life persist over time. See Video Abstract at http://links.lww.com/DCR/A762.

The effects of treatment modality for Graves' disease (GD) were studied with respect to long-term quality of life and present health status. A total of 179 patients with GD were randomized during the period 1983-1990 for treatment with antithyroid drugs, radioiodine, or surgery. A 36-item Short Form Health Status Survey questionnaire and specific questions for GD were sent to patients 14-21 years after randomization. Present medical records, and clinical and laboratory status were recorded. No major significant differences in quality of life among the three treatments were observed. Compared to a large Swedish reference group, all treatment groups had significantly lower scores for vitality (p < 0.05). The Mental Component Summary was lower for both the young medical, young surgical, and the older medical group (p < 0.05). Radioiodine-treated patients had a lower General Health score. Young medical patients (<35 years) had lower Mental Health scores (p < 0.05). There was also a strong trend, which barely met statistically significance, for older surgical and radioiodine groups for lower Mental Component Summary. GD patients have, compared with a large Swedish reference population, diminished vital and mental quality of life aspects even many years after treatment. The quality-of-life scores were not different among the three treatment modalities.

Graves' disease (GD) is an autoimmune condition with elevated thyroid hormone levels and symptoms suggesting an affected brain. These symptoms often resolve with treatment but, for some patients, GD results in a long period of reduced wellbeing. The overall aim of this thesis is to characterize the consequences of GD with a special focus on the brain. Three studies were conducted with data from questionnaires and clinical assessments of patients with GD in both the hyperthyroid and the euthyroid phase. Paper I was a longitudinal cohort study that assessed long-term treatment results 6 10 years after the onset of GD. Among 1186 included patients, the 774 who were initially treated with antithyroid drugs had a 40% chance of being euthyroid without thyroid medication at follow-up. One in four patients did not feel fully recovered. Paper II was a longitudinal case-control study designed to characterize affective and cognitive symptoms in 65 premenopausal women with newly diagnosed untreated GD. At onset of GD, the patients were significantly more affected with depression, anxiety, and mental fatigue compared to controls. At follow-up after 15 months, these symptoms remained in a significant proportion of patients. Patients with eye symptoms or a history of psychiatric conditions were more likely to be affected with brain-related symptoms. Paper III was a longitudinal case-control study of 65 premenopausal women with newly diagnosed untreated GD designed to investigate the effect of GD on hippocampal volumes. At onset of GD, hippocampus and amygdala volumes of the patients were smaller compared to controls. These brain structures became larger with treatment and, after 15 months, only the left amygdala remained smaller than in controls. At inclusion, there was an inverse correlation between thyroid-stimulating hormone receptor antibody (TRAb) and the volumes of both amygdalae and the right hippocampus. There were also inverse correlations between TRAb and free triiodothyronine recovery and the recovery of most of the four assessed brain volumes. GD is a condition where a minority of patients can hope for a long-lasting restored thyroid function. A large proportion of GD patients do not feel recovered after 8 years. Mental fatigue is an important concept for understanding the brain-derived symptoms in GD. In summary, the studies demonstrate that Graves' hyperthyroidism has unexpected long-term consequences for many patients, provide extensive new data on the serious and chronic nature of GD, and show for the first time that GD is accompanied by reversible brain changes.

Restricted perioperative intravenous fluid administration does not reduce length of stay in a fast-track protocol.

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