Red flag symptoms
- Significant unexplained weight loss
- Lymphadenopathy with features of malignancy
- Other features of malignancy - haemoptysis, dysphagia, rectal bleeding, altered bowel habit, breast lump, postmenopausal bleeding (also see below, NICE guidance on suspected cancer)
- Localising or focal neurological signs
- Carbon monoxide poisoning
- Suicidal ideation
'Tired all the time' (TATT), a common yet nebulous symptom, can be difficult to manage, with numerous differentials and the potential to miss serious illness.
However, nearly three-quarters of TATT episodes are isolated and will improve with time and careful communication.2Clarifying the patient's concerns and expectations early may help to avoid progression to chronic fatigue.3
In primary care we aim to distinguish between physical, psychological and lifestyle-related causes whilst at the same time excluding serious pathology. Taking a good history will be essential to narrowing down a potentially enormous array of differentials, all of which cannot be covered here. Specific points to consider include:
- Appetite - loss can suggest serious pathology, but a poor diet and inadequate hydration can also cause fatigue.
- Menstruation - menorrhagia leading to anaemia, oligo/amenorrhoea (for example, due to menopause, pregnancy).
- Neurological symptoms - Parkinson's, MS, neurodegenerative conditions.
- Polyuria/nocturia - diabetes, kidney disease.
- Recent illness, risk factors for chronic infection such as TB, HIV or hepatitis.
- Symptoms of inflammatory or autoimmune conditions such as thyroid disease, Addison's, coeliac disease, inflammatory bowel disease.
- Symptoms or past history of chronic disease such as COPD, ischaemic heart disease, liver disease, chronic skin conditions.
- Symptoms of anxiety, depression.
- Sleep patterns - night shifts, frequent travel, stress, sleep apnoea, restless legs, allergic rhinitis, cough, GORD.
- Weight changes - being overweight or obese can in itself cause tiredness. Being underweight may be a direct or indirect cause (for example, due to malignancy, hyperthyroidism, or eating disorder).
- Family history - cancer, diabetes, thyroid and autoimmune disease.
- Social history - smoking, alcohol, caffeine, drugs, carbon monoxide poisioning, stressors (such as childcare, relationship problems, other significant life events).
- Occupational history such as asbestos exposure, working hours.
- Travel, insect or tick bites - consider tropical infection or Lyme disease.
Questions to ask
- What exactly does the patient mean by 'tired'?
- What is 'all the time'? Duration, pattern, diurnal variation
- What is the patient's usual level of functioning and have there been any previous episodes of fatigue? Beware, an active elderly person who suddenly loses energy may have serious pathology
- What is a typical day in the patient's life? What is the effect of their tiredness on daily activities?
- Are there any associated symptoms? Conduct a quick systems review.
- How is the patient's mood?
- Ask the patient: 'Is there anything that you think may have caused this?'
Important! An active elderly person who suddenly loses energy may have serious pathology
- General appearance, for example pallor, oedema, jaundice, lymphadenopathy, clubbing, gait, affect
- Weight, height and BMI
- Blood pressure and temperature
- Pulse (rate, rhythm, character)
- Rest of examination guided by history
Investigations may be delayed for four weeks4 unless there are red flags, or a suggestion of an atypical or specific cause.
Investigations in primary care may include:
- Urinalysis: infection, glucose, protein, blood
- Initial blood tests: FBC (plus ferritin in women of childbearing age or if other risk factors for iron deficiency), glucose, TSH and ESR
- Others if clinically indicated: U&Es, LFTs, CRP, Epstein-Barr virus serology, hepatitis and HIV serology, calcium, coeliac screen, creatinine kinase, PSA, CA-125, 5,6 ECG, CXR, spirometry.
If initial tests are normal, reassurance and watchful waiting may help, along with addressing any contributing social, psychological or lifestyle factors. Iron deficiency may be an under-recognised cause of tiredness in menstruating women.7
If ferritin is less than 50 micrograms/L, consider treatment, even if Hb is within normal range. Further management will be guided by clinical and laboratory findings.
When to refer
- If red flags or suspected malignancy
- If symptoms are atypical or progressive and the patient appears unwell
- If a rare or serious cause is suspected or identified that could not be managed in primary care
- If there is diagnostic uncertainty and the patient would benefit from a specialist assessment
- Check diagnostic criteria for chronic fatigue syndrome (CFS) if symptoms persist beyond four months8 and consider referral to a specialist CFS clinic
NICE guidance on suspected cancer
NICE recommends the following in people who present with persistent or unexplained fatigue in primary care:6
|Symptom and specific features||Possible cancer||Recommendation|
|Fatigue (unexplained), 40 and over, ever smoked||Lung or mesothelioma||Offer an urgent chest X-ray (to be performed within 2 weeks)|
|Fatigue (unexplained), 40 and over, exposed to asbestos||Mesothelioma||Offer an urgent chest X-ray (to be performed within 2 weeks)|
|Fatigue with cough or shortness of breath or chest pain or weight loss or appetite loss (unexplained), 40 and over||Lung or mesothelioma||Offer an urgent chest X-ray (to be performed within 2 weeks)|
|Fatigue (persistent) in adults||Leukaemia||Consider a very urgent full blood count (within 48 hours)|
|Fatigue (unexplained) in women||Ovarian||Carry out tests in primary care*
Measure serum CA125 in primary care*
|*The recommendations for ovarian cancer apply to women aged 18 and over.|
- Dr Shah is a GP, primary care tutor and and public health associate in Oxford
- NHS Clinical Knowledge Summaries. Tiredness/fatigue in adults. 2015.
- Kenter EGH, Okkes IM, Oskam SK et al. Tiredness in Dutch family practice. Fam Pract 2003; 20(4): 434-40.
- Nijrolder I, Van der Windt D, Van der Horst H. Prediction of outcome in patients presenting with fatigue in primary care. Br J Gen Pract 2009; 59(561): e101-9.
- Koch H, Van Bokhoven MA, Ter Riet G 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 Pract 2009; 59(561): e93-100
- Hamilton W, Watson J, Round A. Investigating fatigue in primary care. BMJ 2010; 341(aug24_2): c4259.
- National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. 2015
- Vaucher P, Druais P-L, Waldvogel S et al. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. Can Med Assoc J 2012; 184(11): 1247-54.
- National Collaborating Centre for Primary Care. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy). 2007.
This is an updated version of an article that was first published in October 2015.