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Table 4 Further investigations in patients with chronic fatigue of unknown cause

From: Investigating unexplained fatigue in general practice with a particular focus on CFS/ME

Clinical Symptoms/Signs Additional investigations
Evidence of Connective Tissue Disease suggested by Raynaud’s phenomenon, mouth ulcers, photosensitive rash, serositis, synovitis, Anti-nuclear antibody assessment on Hep2 cells, antibodies to ENA and dsDNA. Rheumatoid factor analysis and anti-CCP antibodies
Muscle tenderness or history of significant exercise related cramps Creatine Kinase, Lactic dehydrogenase, Liver function tests. Consider EMG and possibly muscle biopsy. Referral for late presenting inherited muscle or glycogen storage diseases.
Widespread aches and pains especially in older women Serum calcium and magnesium estimation and DEXA scan for osteoporosis and hyperparathyroidism. Serum immunoglobulin assessment in basic panel will check for myeloma.
Addison’s/Cushings disease Synacthen/Dexamethasone suppression test. Random cortisol levels can be reduced in CFS/ME and synacthen is advised. Cortisol awakening response is blunted in CFS/ME and might relate to the exacerbation of fatigue in the morning with difficulty getting up in some patients.
Tick bites with erythematous rashes and arthralgia and fatigue Serology for Lyme disease – care with interpretation of results and particularly with results from non-approved laboratories. Lyme disease is rare in the UK especially in areas without deer populations.
Neurological abnormalities, reduced mental acuity and progressive confusion, leg weakness and bladder/bowel problems MRI/CTscan of brain for cerebral atrophy, ischaemic areas, plaques of demyelination, tumours in frontal lobes/para-saggital area and possible Arnold Chiara malformation. Consider also neuropsychological testing.
Intolerance of prolonged standing, recurrent syncope/presyncope, tachycardia within 10 min of standing or marked hypotension on standing with tachycardia. Tilt table testing for autonomic dysfunction and further evaluation for postural orthostatic tachycardia
‘Clicky’ joints with previous dislocation(s), early stretch marks and easy bruising Consider referral for formal evaluation of an underlying or complicating joint hypermobility syndrome.
Significant sleep disturbance Sleep studies. Frequent sleep arousals can cause marked daytime fatigue.