Overview of conditions commonly associated with fatigue

Fatigue is a feature of many conditions and presentations in primary careMaisel, 2021. A definitive diagnosis can be made in a half to two-thirds of patients who present with fatigue in general practiceMacKean, 2016Nijrolder, 2009Okkes, 2002.

Fatigue is frequently associated with psychosocial or environmental factors (eg occupational or financial stress, family conflict)Murtagh, 2018Stadje, 2016. The demands of a busy life can lead to fatigue at any age, from parents who juggle various roles to children with multiple extracurricular activities. People may have unreasonable expectations of what can fit into their day, and fatigue may be a ‘normal’ response. Presentation with fatigue may also be a plea for help, or a consequence of bereavement.

Behavioural factors such as excessive alcohol intake, substance use, lack of exercise and poor diet often result in fatigueBultmann, 2002Murtagh, 2018. Ask about sleep practices (including night-time technology use), diet and lifestyle. A trial of a week or two without caffeine may be worthwhile in frequent users as caffeine can interfere with sleepClark, 2017, although headaches may be problematic during withdrawal.

Medical diagnoses most commonly found in patients with fatigue include psychiatric disorders (eg depression, anxiety), sleep disorders, viral infection, anaemia, diabetes and thyroid disordersFavrat, 2021Galland-Decker, 2019Murtagh, 2018Stadje, 2016. In one systematic review ¹ of studies on people reporting tiredness, depression was the diagnosis in 18.5%, serious somatic disease in 4.3%, and anaemia in 2.8%.

Even in patients with pre-existing fatigue, a recent worsening of fatigue can be the presenting symptom of a serious and potentially treatable underlying condition.

Medical conditions commonly associated with fatigue include:

• depression—may not be overt, so the diagnosis may be missed, especially in those with coexisting physical illness or somatic complaints, and fatigue of longer duration. Depression is a very common comorbidity in people with chronic disease
• anxiety—can cause or contribute to fatigue, as well as be exacerbated by fatigue. Anxiety can also be a comorbidity of conditions that present with fatigue. Assessment should take into account these complexities and the potential for overinvestigation, which may exacerbate patient distress
• anaemia—may present with fatigue associated with pallor or shortness of breath on exertion. Causes include blood loss, deficiency of iron or vitamin B₁₂, and bone marrow disorders
• iron deficiency—even in the absence of anaemia, iron supplementation may improve fatigue in patients with low ferritin concentration²Houston, 2018. Causes of iron deficiency include inadequate dietary intake, occult blood loss, increased physiological requirements for iron (eg during pregnancy), coeliac disease and bariatric surgeryBalendran, 2021
• vitamin B₁₂ deficiencyLangan, 2017
• sleep-related disorders, including
  • obstructive sleep apnoea in adults
  • sleep-disordered breathing in children
  • insomnia in adults
  • sleep problems in children and adolescents
  • advanced sleep–wake phase disorder
  • delayed sleep–wake phase disorder
• endocrine and metabolic disorders, including
  • thyroid disorders
  • parathyroid disorders (eg hyperparathyroidism)
  • diabetes—fatigue may be associated with suboptimal glucose levels in patients with known or undiagnosed diabetes
  • Adrenal insufficiency
  • haemochromatosis
  • obesity
• kidney disease—mild chronic kidney disease is generally asymptomatic, but more severe disease can present with fatigue and should be considered particularly in those with hypertension, diabetes or obesityKidney Health Australia, 2020
• heart failure—usually presents with dyspnoea or oedema, but these can be missed if the patient’s presenting complaint is fatigue. Consider in older people who withdraw from usual activities or complain of a general lack of energy
• respiratory conditions, including
  • chronic obstructive pulmonary disease
• infections, including
  • viral hepatitis
  • human immunodeficiency virus (HIV) infection
  • influenza
  • tuberculosis
  • coronavirus disease (COVID-19)
  • Epstein–Barr virus infection (infectious mononucleosis)
  • cytomegalovirus (CMV) infection
  • Q fever
  • leptospirosis
• neuromuscular conditions, including
  • multiple sclerosis
  • Parkinson disease
  • after ischaemic or haemorrhagic stroke
• autoimmune and inflammatory disorders, including
  • fibromyalgia
  • rheumatoid arthritis
  • systemic lupus erythematosus
  • polymyalgia rheumatica and giant cell arteritis
• malignancy—although malignancy is relatively rare compared with other causes of fatigue (especially in the absence of red flags and other risk factors) it is highly associated with fatigue during all stages of illness. Fatigue can persist even after cancer treatment is completeAl Maqbali, 2021 (see Fatigue in patients with pre-existing conditions)
• deconditioning following a period of inactivity or reduced activity
• convalescence following surgery
• coeliac diseaseTherrien, 2020, food intolerance
• drug effects or interactions, including over-the-counter and complementary medicines and illicit drugs; see History and examination in fatigue for a list of medications that can cause or contribute to fatigue.

There is emerging information about potential long-term effects in patients who have had coronavirus disease (COVID-19); it appears some can develop significant postviral fatigue along with other symptomsCrook, 2021. At the time of writing, there is no evidence to guide specific treatment. The same treatment principles apply as for persistent unexplained fatigue. Patients should be reviewed regularly and offered support and advice on symptom management. See also the Royal Australian College of General Practitioners (RACGP) advice on supporting patients after acute COVID-19 illness.