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.
Study Type
OBSERVATIONAL
Enrollment
180
Department of Endocrinology, Sahlgrenska University Hospital
Gothenburg, Sweden
RECRUITINGIdentifying autoantibodies targeting antigens occurring in the brain that are higher in Graves' disease complicated by mental fatigue than in Graves' disease not complicated by mental fatigue
Each group will be analysed in arrays for antibodies targeting 42000 human proteins (ScilifeLabs, Stockholm). Proteins binding to antibodies in mental fatigue patients will be screened against the Human Protein Atlas (www.proteinatlas.org) and the Allen brain map (www.brain-map.org) and those expressed in the brain will be compared between groups.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Identifying autoantibodies targeting antigens occurring in the brain that are higher in Graves' disease complicated by mental fatigue than in thyroid healthy controls without mental fatigue
Each group will be analysed in arrays for antibodies targeting 42000 human proteins (ScilifeLabs, Stockholm). Proteins binding to antibodies in mental fatigue patients will be screened against the Human Protein Atlas (www.proteinatlas.org) and the Allen brain map (www.brain-map.org) and those expressed in the brain will be compared between groups.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Identifying autoantibodies targeting antigens occurring in the brain that are higher in Graves' disease not complicated by mental fatigue than in thyroid healthy controls without mental fatigue
Each group will be analysed in arrays for Ab targeting 42000 human proteins (ScilifeLabs, Stockholm). Proteins binding to Ab in MF patients will be screened against the Human Protein Atlas (www.proteinatlas.org) and the Allen brain map (www.brain-map.org) and those expressed in the brain will be compared between groups.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Thyroid autoantibodies compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
Levels of thyroid autoantibodies will be analysed with the standard method of the laboratory at Sahlgrenska University Hospital.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Cytokines compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
Levels of cytokines will be analysed with the standard method of the laboratory at Sahlgrenska University Hospital.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Biomarkers indicating organic and structural nerve damage compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
Biomarkers will be analysed with the standard method of the laboratory at Sahlgrenska University Hospital.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Autoantibodies to other g-protein coupled receptors compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
Levels of autoantibodies to g-protein coupled receptors will be measured using enzyme-linked immunosorbent assays
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Prevalence of endocrine ophthalmopathy in Graves' complicated by mental fatigue compared to prevalence of endocrine ophtalmopathy in Graves' not complicated by mental fatigue
Prevalence defined as endocrine ophthalmopathy that has required assessment/and or follow up at ophthalmologist.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Self evaluated quality of life in relation to ophthalmopathy will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire the Graves' Ophthalmopathy Quality of Life Questionnaire (GO QoL).
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Self evaluated quality of life in relation to thyroid symptoms will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire Thyroid-specific Patient-Reported Outcome short-form (ThyPro 39)
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Self evaluated quality of life and well being will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire Psychological General Well Being index (PGWB)
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Self evaluated symptoms of anxiety and depression will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire the Comprehensive Psychopathological Rating Scale (CPRS).
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Self evaluated stress will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire Perceived Stress Scale (PSS-14).
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Coping strategies will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire Brief cope.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Optimistic self-beliefs to cope with difficulties in life will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire General self efficacy.
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Personality traits will be compared between patients with Graves' with and without mental fatigue and to healthy controls
Evaluated by the validated questionnaire NEO Five-Factor Inventory-3 (NEO-FFI-3).
Time frame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
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