Graves' Disease; Aspects on Orbitopathy and Bone Metabolism

Sammanfattning: Graves' disease (GD) is an autoimmune disorder that affects the thyroid gland, with an annual incidence of 21 in 100,000 individuals in Sweden. Graves' orbitopathy (GO) is relatively common in GD and affects 50% of all patients to varying degrees of severity, with severe forms affecting 3–5% of patients. Early diagnosis and treatment of GO are crucial to avoid developing complications from the severe forms of GO. Diagnosis and treatment of GO are still challenging in many complicated cases; thus, new biomarkers are required for improved management. Thyroglobulin (Tg) is a glycoprotein produced by the follicular cells in the thyroid gland whose connection to GO has not been clarified. Measurement of thyroid stimulating immunoglobulins (TSI) is described as a more precise method than the traditional third-generation immunoassay of TSH receptor antibodies (TRAb), for improved diagnosis and management of GD. Vitamin D and bone health in GD have been investigated in different studies with conflicting results. This thesis aimed to explore the role of new biomarkers in the management of GO and to study the impact of GD on bone health. In Papers I–III, we studied 30 consecutive patients with de novo GD. Our studies show that higher levels of Tg are associated with a higher risk of developing GO. However, TSI was highly correlated to TRAb in GD, and it was not more precise than TRAb in the management of GO. No vitamin D deficiency was observed, but data confirm that hyperthyroidism has a negative effect on bone health. During treatment of GD, bone health improved over a two-year follow-up period. In Paper IV, a total of 2,134 patients with GD were included in an investigation 16–18 years after inclusion regarding the risk of developing skeletal complications. There were no increased fracture rates in patients with GD compared to up to ten controls from the general population. However, male patients older than 52 years may have an increased risk of vertebral fractures.