Exploring Immunological Markers Associated With Mental Fatigue in Graves' Disease

Exploring Immunological Markers in Blood and Cerebrospinal Fluid Associated With Mental Fatigue in Euthyroidism After Graves' Disease- a Cross Sectional Study

Mental fatigue occurs in many diseases and the reasons are mostly unknown. The investigators hypothesize that remaining mental fatigue after restored hyperthyroidism in Graves' disease is an autoimmune complication. The aim of this study is to explore immunological markers possibly associated with mental fatigue in Graves' disease, which the investigators plan to validate in another study (ImmunoGraves wp 2).

Using a cross-sectional study design, mental fatigue is scored using a questionnaire to find 60 patients with and 60 without mental fatigue 15-60 months after diagnosis of Graves disease. The patients and 60 thyroid healthy controls without mental fatigue are assessed for thyroid hormones, quality of life, anxiety and depression, self-evaluated stress, coping strategies, eye symptoms and background variables. SciLifeLab in Stockholm, the national facility for autoimmune profiling, has pre-set large arrays including 42000 human proteins. Serum and cerebrospinal fluid will be separately pooled and analysed for a subgroup of patients with or without mental fatigue and for a subgroup of the control group. Proteins that preferably bind to antibodies in sera and/or cerebrospinal fluid from Graves' patients with mental fatigue in comparison to non-mental fatigue patients, will be screened against the Human Protein Atlas and the Allen brain map to identify those proteins that are expressed in the brain. Antibodies at higher concentration in the mental fatigue pools compared to the group without mental fatigue will be selected for further analyses on an individual level in the whole cohort together with antibodies targeting g-protein coupled receptors, thyroid autoantibodies, cytokines and biomarkers indicating organic and structural nerve damage.

Inclusion Criteria

• If patient: Graves' disease with positive TSH-receptor antibodies and thyroid hormones above the upper reference limit at diagnosis
• Diagnosis15 to 60 months ago. If recidive both episodes must have occurred within 15 months to 60 months.
• Thyroid hormones within normal range without anti thyroid drugs
• If control: No thyroid disease
• Patient and control without mental fatigue: Mental Fatigue Score ≤8 (cut off 10.5)
• Patient with mental fatigue: Mental Fatigue Score >13 and debut of symptoms of mental fatigue in parallel with debut of Graves' disease, without other obvious cause

Exclusion Criteria

• Person unable to follow protocol
• Multiple sclerosis, myalgic encephalomyelitis/chronic fatigue syndrome, any other neurological disease
• Traumatic brain injury with unconsciousness
• Other disease strongly associated with fatigue
• Pregnancy and breast-feeding
• On-going or recent systemic treatment with steroids
• Radioiodine therapy within the last 18 months