Red flag symptoms: Tired all the time

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

History

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

Examination

• 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

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

• Dr Shah is a GP, primary care tutor and and public health associate in Oxford

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References

1. NHS Clinical Knowledge Summaries. Tiredness/fatigue in adults. 2015.
2. Kenter EGH, Okkes IM, Oskam SK et al. Tiredness in Dutch family practice. Fam Pract 2003; 20(4): 434-40.
3. 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.
4. 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
5. Hamilton W, Watson J, Round A. Investigating fatigue in primary care. BMJ 2010; 341(aug24_2): c4259.
6. National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. 2015
7. 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.
8. National Collaborating Centre for Primary Care. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy). 2007.