What initial assessments should I perform for a patient presenting with unexplained fatigue?

For a patient presenting with unexplained fatigue, initial assessment should include a comprehensive clinical evaluation encompassing a detailed history, physical examination, and targeted investigations to exclude underlying causes.

History and symptom assessment should explore the duration, severity, and impact of fatigue on daily activities, presence of associated symptoms such as unrefreshing sleep, post-exertional malaise, cognitive difficulties, mood changes, and any potential triggers or exacerbating factors ¹,². It is important to assess for symptoms suggestive of specific conditions such as chronic fatigue syndrome (CFS), multiple sclerosis (MS), inflammatory bowel disease, or malignancy ¹,²,³,⁴,⁵.

Physical examination should focus on general signs of systemic illness, neurological examination, and assessment for signs of anaemia, thyroid disease, or other relevant abnormalities ¹,²,⁶.

Initial investigations should include basic blood tests to exclude common reversible causes: full blood count, urea and electrolytes, liver function tests, thyroid function tests, inflammatory markers (erythrocyte sedimentation rate or plasma viscosity, C-reactive protein), serum ferritin, HbA1c, and urinalysis for protein, blood, and glucose ¹,². Additional tests such as vitamin B12, folate, vitamin D, coeliac screening, creatine kinase, and 9am cortisol may be considered based on clinical judgment ¹,².

Consideration of red flags is essential, especially in patients aged 40 and over with unexplained fatigue and risk factors such as smoking or asbestos exposure, where urgent chest X-ray is recommended to exclude lung cancer or mesothelioma ⁵. Persistent fatigue with systemic symptoms may warrant urgent full blood count to exclude haematological malignancies ⁵.

Psychosocial assessment should evaluate for anxiety, depression, sleep disturbance, and stress, as these commonly contribute to fatigue and may require concurrent management ¹,³,⁶.

Explanation and support should be offered to patients, linking physical and psychosocial factors, and providing information on sleep hygiene and sources of support ¹.

Referral to secondary care or specialist services should be considered if an underlying cause is suspected that cannot be managed in primary care, or if diagnostic criteria for CFS are met with symptoms persisting beyond 3 months ¹,².