Fatigue: the Australian GP workup — systematic investigation of tiredness

What fatigue is — and why it matters

Fatigue is a subjective sense of tiredness, exhaustion, or lack of energy that is disproportionate to exertion and not restored by ordinary rest. It is the most common symptom presenting to Australian GPs — appearing in 10–25% of consultations and affecting approximately 30% of Australian adults for at least two weeks in any given year.

Three clinical distinctions matter immediately: fatigue is persistent tiredness without restoration by sleep; sleepiness is the tendency to fall asleep (pointing to obstructive sleep apnoea, narcolepsy, or sleep restriction); and weakness is objective loss of muscle power on examination (pointing to neuromuscular disease). Each has a different investigative pathway.

The GP’s role is not to assign a vague label — it is to systematically exclude reversible causes, identify any chronic fatigue syndrome, and coordinate ongoing care if no single cause is found.

A. Core clinical — the AU general-practice framework

Classification by duration

Per the RACGP approach to fatigue:

• Acute fatigue — less than 1 month; commonly reactive (viral illness, sleep restriction, acute stress); usually resolves spontaneously
• Prolonged fatigue — 1–6 months; requires structured workup
• Chronic fatigue — more than 6 months; broadens the differential to include ME/CFS, Long COVID, occult malignancy, autoimmune, and endocrine conditions

History: where the diagnosis lives

A careful history is the most productive diagnostic step in fatigue assessment.

Onset and pattern. Sudden onset after an identified illness (COVID-19, Epstein-Barr virus, Q fever, Ross River virus) suggests a post-infective fatigue syndrome. Gradual onset without a clear precipitant broadens the differential considerably. A weekly pattern that improves on weekends points to sleep restriction or occupational contributors.

Post-exertional malaise (PEM) screen. Ask specifically: “Do your symptoms worsen 12–48 hours after physical or mental activity, lasting at least 24 hours?” This is the cardinal discriminator for ME/CFS and Long COVID per NICE NG206. Patients do not always volunteer PEM; active screening at every consultation is essential.

B-symptoms. Unexplained fever, drenching night sweats, and unintentional weight loss exceeding 10% of body weight over 6 months are red flags requiring urgent malignancy and chronic infection workup rather than routine review.

Sleep screen. Snoring, witnessed apnoeas, morning headaches, and daytime sleepiness point to obstructive sleep apnoea. The STOP-BANG questionnaire is a validated screening tool; scores of 3 or above warrant formal sleep study referral. Insomnia (difficulty initiating or maintaining sleep) is a separate but related contributor to fatigue.

Mood screen. Depression and anxiety are screened for routinely using validated tools: PHQ-9 for depression, GAD-7 for anxiety. Comorbid mood disorders are common in chronic fatigue, but they are never assumed to be the sole explanation without physical workup. Diagnostic overshadowing — attributing everything to a mood disorder without investigating physical causes — is a documented harm in fatigue management.

Medication review. Fatigue is a recognised adverse effect of beta-blockers, sedating antihistamines, benzodiazepines, opioids, antiepileptics, some antidepressants, and antipsychotics. Any new prescription in the preceding 3 months is always reviewed for temporal correlation.

Menstrual history. Heavy menstrual bleeding is a common and frequently underestimated driver of iron deficiency anaemia and fatigue in women of reproductive age.

Physical examination

The examination is targeted at reversible causes and red flags:

• Vitals: including postural blood pressure measurement — a drop of 20 mmHg systolic or 10 mmHg diastolic on standing suggests autonomic dysfunction, adrenal insufficiency, or volume depletion
• Pallor of conjunctivae and mucous membranes indicating anaemia
• Thyroid — goitre, palpable nodule, or bruit
• Lymphadenopathy — particularly supraclavicular (Virchow’s node raises concern for gastrointestinal and lung malignancy), axillary, and inguinal nodes
• Skin pigmentation — patchy buccal and palmar crease pigmentation are features of Addison’s disease
• Neurological — muscle power, deep tendon reflexes (the slow relaxation phase is characteristic of hypothyroidism), gait

First-line investigations

The standard fatigue panel, aligned with RACGP guidelines and supported by Cochrane evidence, includes:

1. FBC — checks for anaemia, leucopenia (autoimmune conditions, HIV), and lymphocytosis
2. Iron studies and serum ferritin — iron deficiency is the most common reversible cause of fatigue; ferritin below 30 µg/L is symptomatic even without frank anaemia in many patients
3. B12 and folate — particularly relevant in vegans, older adults, patients taking metformin, and those with malabsorption
4. UEC — renal failure, hyponatraemia (which may indicate adrenal insufficiency or SIADH)
5. Fasting glucose or HbA1c — undiagnosed type 2 diabetes is a reversible cause of fatigue
6. Liver function tests — hepatitis, non-alcoholic fatty liver disease, alcohol-related liver disease
7. Thyroid stimulating hormone (TSH) — hypothyroidism occurs in 3–5% of adults; TSH is the most reliable single screening test
8. CRP and ESR — screening for occult inflammation and malignancy
9. 25-OH vitamin D — in patients with recognised risk factors (covered dress, dark skin pigmentation, malabsorption, anticonvulsant use, limited outdoor exposure, older adults in residential care); Choosing Wisely Australia recommends against routine testing in low-risk individuals
10. Urinalysis — infection, proteinuria, glycosuria

Beta-HCG is added for any reproductive-age patient with new symptoms.

B. Investigation pitfalls — what not to order

Over-investigation is as harmful as under-investigation. NPS MedicineWise and Choosing Wisely Australia identify common pitfalls in fatigue workup:

Routine ANA in unselected patients. Approximately 10% of healthy individuals test positive for antinuclear antibody (ANA), generating patient anxiety, cascade specialist referral, and unnecessary further testing. ANA is appropriate only when clinical features of connective tissue disease are present — rash, arthralgia, Raynaud’s phenomenon, oral ulcers, sicca symptoms, or alopecia.

Routine vitamin D in low-risk patients. Vitamin D deficiency is a reversible contributor to fatigue, but the RCPA via Choosing Wisely flags routine testing in adults without recognised risk factors as unhelpful and not cost-effective.

“Adrenal fatigue” salivary cortisol curves. This naturopathic construct has no diagnostic validity. The recognised medical condition — adrenal insufficiency (Addison’s disease) — is assessed via 8 am serum cortisol, with short Synacthen testing when borderline, as outlined in the Endocrine Society guideline. The Endocrine Society explicitly does not recognise “adrenal fatigue” as a medical diagnosis.

Private-laboratory fatigue panels. Hair-mineral analysis, food-intolerance IgG testing, and proprietary fatigue panels from private laboratories have no evidence base, are identified by RACGP as inappropriate, and deflect clinical attention from evidence-based investigation.

Graded exercise therapy when PEM is present. Prescribing progressively increasing exercise to a patient with post-exertional malaise risks triggering prolonged symptom relapses. This is now explicitly contraindicated in ME/CFS and Long COVID with PEM per NICE NG206.

C. ME/CFS, Long COVID, and post-viral fatigue

Post-exertional malaise

Post-exertional malaise (PEM) is a disproportionate worsening of fatigue, cognitive difficulties, pain, and other symptoms occurring 12–48 hours after physical or cognitive exertion and lasting at least 24 hours. Per NICE NG206 (2021), PEM is the cardinal feature distinguishing ME/CFS and Long COVID from other fatigue syndromes. Without active screening using validated tools, PEM is consistently missed in general practice consultations.

ME/CFS

ME/CFS (myalgic encephalomyelitis / chronic fatigue syndrome) is a multisystem condition characterised by: PEM (mandatory feature), unrefreshing sleep, cognitive impairment (“brain fog”), and orthostatic intolerance — symptoms that worsen on standing. Approximately 250,000 Australians are affected, per Emerge Australia. Diagnosis is clinical after exclusion of other causes — no single diagnostic test confirms ME/CFS.

Graded exercise therapy (GET) — once widely promoted — is now explicitly not recommended in ME/CFS with PEM, following overwhelming evidence of harm. Energy pacing — living within an individual’s energy envelope to avoid post-exertional crashes — is the cornerstone of management. Cognitive behavioural therapy is a useful adjunct for mood comorbidity and adjustment to chronic illness, but is not a curative treatment for the biological features of ME/CFS.

Long COVID

Long COVID is persistent fatigue, cognitive impairment, breathlessness, and other symptoms more than 12 weeks after SARS-CoV-2 infection, where symptoms are not explained by an alternative diagnosis, per NICE NG188. Fatigue with PEM is the most common Long COVID presentation. Approximately 5–10% of people who had COVID-19 develop Long COVID at 12 weeks. The NHMRC is developing Australia’s first national ME/CFS guideline, which will include Long COVID fatigue management.

Post-infective fatigue syndromes

Post-infective fatigue syndromes — following EBV, CMV, Q fever, Ross River virus, parvovirus B19, and now COVID-19 — are well-recognised in Australian general practice. Most resolve within 6 months. Beyond 6 months, ME/CFS criteria may be met. Investigation at the acute stage includes specific serology; monitoring for resolution versus chronification guides further management.

D. Australian operations

MBS billing

The fatigue consultation typically attracts MBS item 36 (Level C, 20 minutes) or item 44 (Level D, 40+ minutes), reflecting the complexity of a structured fatigue workup. The first-line blood panel is rebatable via standard pathology MBS items. Sleep study referral for obstructive sleep apnoea workup uses MBS item 12203.

When comorbid depression or anxiety is identified, a Mental Health Care Plan (MHCP, MBS item 2715 for preparation, item 2717 for review) provides 10 subsidised psychology sessions per calendar year under the Better Access initiative.

Patients with chronic fatigue lasting more than 6 months with documented functional impact are eligible for a General Practice Comprehensive Care Plan (GPCCMP, MBS item 965), enabling direct referral to allied health professionals including occupational therapists, physiotherapists, and dietitians without re-referral.

For Aboriginal and Torres Strait Islander patients, the 715 ATSI Health Assessment (MBS item 715) provides a structured preventive framework within which fatigue assessment fits appropriately.

PBS medications relevant to fatigue management

• Ferrous sulfate or fumarate — general PBS listing for iron deficiency anaemia
• Intravenous iron carboxymaltose (Ferinject) — Authority Required (Streamlined) for confirmed iron deficiency with intolerance of or failure to respond to oral therapy
• Levothyroxine — general PBS listing for confirmed hypothyroidism
• Hydroxocobalamin (B12) intramuscular — general PBS listing for B12 deficiency
• Antidepressants (SSRIs, SNRIs) — general PBS listing for comorbid depression and anxiety

Modafinil is PBS-listed for narcolepsy only; it is not available via PBS for chronic fatigue or ME/CFS.

Sick certificates and social supports

Patients with prolonged or chronic fatigue affecting work capacity are entitled to appropriate medical certificates. The duration should reflect clinical reality — a few days is often insufficient. Where ME/CFS or Long COVID is the working diagnosis, thorough documentation supports NDIS applications for severely affected individuals and Centrelink Sickness Payment or Disability Support Pension assessments for longer-term incapacity.

E. Special populations

Older adults. Fatigue in adults over 65 warrants particular attention to polypharmacy (medication adverse effects are common), anaemia, thyroid dysfunction, occult malignancy, depression (often underrecognised), heart failure, and nutritional deficiencies including B12. Frailty assessment adds important prognostic context.

Pregnancy and postnatal period. Iron deficiency anaemia is common in pregnancy and contributes significantly to fatigue. Postnatal fatigue is multifactorial — sleep deprivation, iron depletion, thyroid dysfunction (postpartum thyroiditis occurs in 5–10% of women), and perinatal depression all require separate evaluation. Thyroid function testing at 6–12 weeks postpartum is reasonable when fatigue is prominent.

Aboriginal and Torres Strait Islander people. The 715 ATSI Health Assessment provides a structured, culturally appropriate framework for fatigue assessment within comprehensive chronic disease prevention checks. Higher rates of chronic disease, iron deficiency, and social determinants of health affect fatigue presentations in this population. Coordination with Aboriginal Community Controlled Health Organisations (ACCHOs) supports culturally safe care.

Adolescents. Post-viral fatigue following COVID-19 or EBV is common in adolescents and can lead to significant school absenteeism. Graded exercise is not appropriate when PEM is present. School re-integration plans benefit from documented medical support.

Healthcare workers. Occupational burnout, shift work, and secondary trauma are important occupational drivers of fatigue in healthcare workers that require acknowledgement alongside physical workup. Referral to Doctors’ Health Advisory Services or peer support programs is appropriate when occupational burnout is identified.

When to escalate

Refer or seek urgent assessment when:

• B-symptoms (fever, night sweats, weight loss exceeding 10% in 6 months), new lymphadenopathy, or organomegaly — urgent malignancy and chronic infection workup
• Suspected adrenal crisis — severe hypotension, hyponatraemia, and hyperkalaemia together — emergency management
• Suicidal ideation — acute mental health crisis pathway
• Rapidly progressive functional decline — including new inability to walk, self-care, or eat
• Persistent elevated ESR (above 50) with unexplained fatigue in adults over 50 — polymyalgia rheumatica or giant cell arteritis workup via rheumatology
• Chronic fatigue unchanged after 3–6 months of structured general-practice workup — specialist physician, infectious diseases, sleep medicine, or immunology referral

What this article is and is not

This is general health information drawn from current Australian general practice guidelines — RACGP clinical resources, Therapeutic Guidelines (eTG), NPS MedicineWise, NICE NG206, and Emerge Australia — and Australian general-practice epidemiology. It is not personal medical advice and does not create a doctor–patient relationship. Assessment and management of fatigue require individual clinical evaluation by a qualified health practitioner.

For Australian consumer resources: Better Health Channel — Fatigue, HealthDirect — Tiredness and fatigue, Emerge Australia.

For mental health support: Beyond Blue 1300 22 4636, Lifeline 13 11 14.

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Sources cited

1. RACGP — Fatigue: a practical approach to investigation and management (Australian Family Physician)
2. NICE NG206 — ME/CFS: diagnosis and management 2021
3. NICE NG188 — COVID-19: managing the long-term effects
4. NPS MedicineWise / Choosing Wisely Australia
5. Cochrane — Routine laboratory testing for unexplained fatigue
6. Therapeutic Guidelines (eTG) — Fatigue
7. NHMRC — Australian guidelines to reduce health risks from drinking alcohol 2020
8. Emerge Australia — ME/CFS clinical resources
9. Better Health Channel (Victoria) — Fatigue
10. HealthDirect — Tiredness and fatigue
11. Bornstein SR et al. — Endocrine Society guideline on adrenal insufficiency. J Clin Endocrinol Metab 2016
12. Drs4Drs — Doctors’ Health Advisory Services Australia