Fatigue/Tired all the Time


Exploration of stressful life events is more likely to be productive than proceeding directly to testing.

About 10% of patients are found to have physical disease, most commonly anaemia, diabetes, or hypothyroidism.

The VAMPIRE trial of primary care patients showed that most patients randomised to postponed blood testing did not return.

Related Clinical Referral Guidelines:


Differential Diagnoses

The many causes of fatigue include:

Red Flags

Patients ≥40 years who have ever smoked, or have history of asbestos exposure:

  • Chest X ray within 2 weeks


In the absence of systemic illness, consider postponing blood testing for one month

Exploration of stressful life events is more likely to be productive than proceeding directly to testing. This strategy will reduce the number of tests, and create fewer false positive results.

If blood tests are performed we recommend initially checking; FBC, PV, HbA1c, TSH. In women of reproductive age also check Ferritin

This is based on weak evidence and clinicians may wish to expand on this range of tests, however this will increase the risk of false positive results.

If initial tests are normal

Watchful waiting is recommended. In the absence of further symptoms second line testing could be delayed until symptoms have persisted for 3 months.

Second line tests should include Renal, LFT, Calcium, CRP, CA125 (females), Coeliac antibodies, Creatine Kinase; and Urinalysis for blood and protein.

CRP and PV are non-specific markers of infection, inflammation or malignancy. CRP is more useful than PV in detecting bacterial infection, however this is an unlikely cause of unexplained fatigue. Normal or only moderately elevated CRP or PV neither rule in, nor rule out serious underlying disease.

Elevated results should prompt an early clinical review focussing on infection, inflammation and malignancy. It may be helpful to repeat the test to see if levels are changing. Testing for myeloma should be approached with caution because detecting monoclonal gammopathy of undetermined significance (MGUS) is more likely than detecting myeloma. The majority of cases MGUS do not progress to myeloma, but the diagnosis is a source of longterm anxiety for the patient. Among patients with unexplained fatigue we only would recommend testing for myeloma if the patient was >50 year and PV >2.0.


Chronic Fatigue Syndrome should not be diagnosed until symptoms have persisted beyond 4 months.

​Supporting Information


Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. NICE guideline [CG53].Published: 2007.

Clinical Knowledge Summary. Tiredness / Fatigue in adults. Revised February 2015.

Coeliac disease: recognition, assessment and management. NICE guideline [NG20]. Published: September 2015.

Hamilton W, Watson J, Round A. Investigating fatigue in primary care BMJ 2010; 341 :c4259

Koch H, van Bokhoven MA, ter Riet G, van Alphen-Jager JM, van der Weijden T, et al. Ordering blood tests for patients with unexplained fatigue in general practice: what does it yield? Results of the VAMPIRE trial. Br J Gen Pract2009;59:e93-100.

Suspected cancer: recognition and referral. NICE guideline [NG12]. Published: June 2015.

Watson J, Round A, Hamilton W. Raised inflammatory markers BMJ 2012; 344 doi

Pathway Group

This guideline has been signed off by the Pathology Optimisation Clinical Group on behalf of NEW Devon CCG.

Publication date: April 2017


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