Dear Specialist,
I am seeking advice on the current gold standard for diagnosing Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME/CFS).
Given the continued difficulty in pinpointing a single definitive test, which specific biomarkers or blood tests (such as cortisol levels, inflammatory markers, or mitochondrial function assays) are considered most critical today for differential diagnosis, particularly when ruling out endocrine or autoimmune disorders?
Any guidance on emerging diagnostic protocols would be greatly appreciated.
Thank you for your expert insights.
Diagnosis of ME/CFS is still clinical; there is no single definitive blood or imaging test. The “gold standard” in practice is applying IOM/NICE criteria (fatigue with marked functional reduction, post‑exertional malaise, unrefreshing sleep, plus cognitive impairment and/or orthostatic intolerance) and excluding alternative diagnoses.For labs, the critical role is differential diagnosis, not confirmation of ME/CFS. In routine work‑up you would prioritise:General panel: CBC, ESR/CRP, U&E, LFTs, fasting glucose/HbA1c, ferritin/iron, B12, folate, vitamin D, CK, urinalysis.Endocrine: TSH + free T4 (± free T3), early‑morning cortisol (± dynamic testing if indicated), and additional pituitary/sex hormones only if clinically suggested.Autoimmune: targeted ANA ± ENA, RF/ACPA, thyroid antibodies and others guided by phenotype.Cortisol and HPA‑axis tests are used almost solely to rule out adrenal disease; subtle HPA changes in ME/CFS are not specific enough to diagnose it. Likewise, routine inflammatory markers are usually normal; research cytokine panels, mitochondrial function assays, metabolomics, and epigenetic signatures are promising but remain research‑grade and not part of standard diagnostic protocols.
