Red flag symptoms: Tired all the time

Consider a rare cause if the symptoms are atypical or progressive and the patient appears to be unwell.

Iron deficiency may be a cause of tiredness
Iron deficiency may be a cause of tiredness
  • Unexplained weight loss
  • Lymphadenopathy with features of malignancy
  • Other features of malignancy - haemoptysis, dysphagia, rectal bleeding, altered bowel habit, breast lump, postmenopausal bleeding
  • Features of systemic disease - autoimmune, neurological, cardiovascular
  • Sleep apnoea1

'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.

Reassuringly, however, nearly three-quarters of TATT episodes are isolated and will improve with time and careful communication.2 Clarifying the patient's concerns and expectations as early as possible may help to avoid progression to chronic fatigue.3

Possible causes
  • Iron deficiency anaemia (menstruation)
  • Malignancy
  • Systemic illness
  • Anxiety
  • Depression
  • Social/lifestyle stressors


Physical, psychological and lifestyle-related causes should be distinguished between, while excluding serious pathology. Specific points to consider include:

  • Weight changes - being overweight or obese can in itself cause tiredness. Being underweight may be a direct or an indirect cause (for example, due to malignancy, eating disorder).
  • Appetite - loss can suggest serious pathology, but a poor diet can also cause fatigue.
  • Menstruation - menorrhagia leading to anaemia, oligo/amenorrhoea (for example, due to menopause, pregnancy).
  • Symptoms of hypothyroidism.
  • Polyuria/nocturia - diabetes, renal disease.
  • Recent illness, risk factors for chronic infection such as TB.
  • Symptoms of anxiety, depression.
  • Sleep patterns - night shifts, frequent travel, sleep apnoea, restless legs.
  • Family history - cancer, diabetes, thyroid and autoimmune diseases.
  • Social - alcohol, caffeine, drugs, stressors, for example, children, relationship problems, other significant life events.

Questions to ask

  • What exactly does the patient mean by 'tired'? Drowsiness, shortness of breath, muscle weakness?
  • 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? Beware, an active elderly person who suddenly loses energy may have serious pathology
  • What is the effect on daily activities?
  • Are there any associated symptoms (quick systems review)?
  • Is the patient taking any medication, including antihypertensives, OTC, or herbal preparations?
  • Ask the patient: 'Is there anything that you think may have caused this?'


  • General appearance: pallor of anaemia, oedema, jaundice
  • Weight, height and BMI
  • BP
  • Pulse (rate, rhythm, character)
  • Rest of examination guided by history


Investigations may be delayed for four weeks4 unless there are red flags, or suggestion of an atypical or specific cause.

A recent RCT suggests iron deficiency may be an under-recognised cause of tiredness in menstruating women.5

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, calcium, coeliac screen, creatinine kinase6

If initial tests are normal, watchful waiting may help.

If ferritin less than 50 microgram/L, consider treatment, even if Hb is within normal range. Further management is guided by clinical and laboratory findings.

When to refer

  • If red flags or suspected malignancy, refer via two-week wait
  • Consider a rare cause if symptoms are atypical or progressive and the patient appears unwell
  • Check diagnostic criteria for chronic fatigue syndrome if symptoms persist beyond four months7
  • Dr Shah is a GP and public health specialist in Oxford

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1. NHS Clinical Knowledge Summaries. Tiredness/fatigue in adults - red flags. 2009.
2. Kenter EGH, Okkes IM, Oskam SK et al. Tiredness in Dutch family practice. Data on patients complaining of and/or diagnosed with "tiredness". 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. 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.
6. Hamilton W, Watson J, Round A. Investigating fatigue in primary care. BMJ 2010; 341(aug24_2): c4259.
7. National Collaborating Centre for Primary Care. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy). RCGP, 2007.

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