Table 3 Basic investigations in patients with prolonged fatigue of unknown cause

FBC

Anaemia, polycythaemia, haematological malignancy can all be associated with fatigue. Red cell MCV may indicate need to check ferritin if reduced and vitamin B12 and folate deficiency if raised.

ESR

This is a good test of overall immune activation and a raised level should encourage an assessment of infection, autoimmunity, certain solid organ neoplasms and possible lymphoproliferation.

CRP

A raised level suggests inflammation somewhere. Where the source of the inflammation is not obvious from the history consider the sinuses, urinary tract

Urea, creatinine, electrolytes and Liver Function tests

Dysfunction in both areas can be accompanied by fatigue. There is an interesting association between Gilberts disease and fatigue [81] The mechanism is unknown.

Thyroid function tests

Both hypo and hyper-thyroidism can be accompanied by fatigue. In a small proportion of patients with anti-thyroid peroxidase antibodies but essentially normal T4 and TSH, low dose thyroxine can be helpful.

Autoimmune profile on tissue block

Can help check for Sjogren’s syndrome, early primary biliary cirrhosis and autoimmune hepatitis and atropic gastitris. The latter can be associated with vitamin B12 deficiency. A positive ANA here may encourage further tests of autoimmunity.

Anti-Tissue Transglutaminase (TTg) or endomysial antibodies

Coeliac disease can present with fatigue and without bowel symptoms.

Immunoglobulins and serum protein electrophoresis

Serum immunoglobulins are low in antibody deficiency but raised in chronic inflammation/infection. Both conditions can be accompanied by marked fatigue

Urine dipstick analysis

Simple check for renal inflammation/infection and renal tumours.