About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial population

Patients are recruited from the both previous patients at the Endocrine outpatient Clinic at Sahlgrenska University Hospital in Gothenburg and from advertising. They are invited to a web based screening form where the ones eligible are contacted by study personal and eligibility criteria are checked again. Controls are recruited by the same way and by contacting a random sample from the population registration (based on Swedish social security number). Groups are matched for age, educational level and smoking habits.

Trial design

Design model

Cohort

Time perspective

Cross-sectional

Treatments tested in this trial

Not listed

Trial groups

180 Participants

are grouped into 3 trial groups

Group A: Graves' patients with mental fatigue

Group B: Graves' patients without mental fatigue

Group C: Thyroid healthy controls without mental fatigue

Trial outcomes

Primary outcomes

1

Identifying 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