The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure.
Hulens, Mieke, Dankaerts, Wim, Rasschaert, Ricky et al. · Journal of pain research · 2023 · DOI
Quick Summary
This review explores a possible connection between three conditions—empty sella syndrome, fibromyalgia, and ME/CFS—that may all involve increased pressure from cerebrospinal fluid around the brain and pituitary gland. The authors found that these conditions share similar symptoms (fatigue, pain, headaches, vision problems) and similar hormone imbalances, suggesting that fluid pressure problems might be a common underlying cause worth investigating further.
Why It Matters
This study proposes a testable biological mechanism—CSF pressure dysregulation—that could unify understanding of HPA axis dysfunction in ME/CFS and fibromyalgia. If validated, this hypothesis could redirect research toward identifying and potentially treating elevated intracranial pressure as a treatable feature, rather than viewing these conditions as purely functional or psychiatric.
Observed Findings
Increased cerebrospinal fluid pressure is more prevalent in primary ES, FM, and CFS patients compared to controls.
Multiple shared clinical features exist across the three conditions: fatigue, headaches, migraine, visual disturbances, vertigo, hearing loss, and bodily pain.
Pituitary hormone challenge tests show similar abnormal responses across all three conditions: blunted ACTH, cortisol, GH, LH, and TSH responses, with elevated prolactin.
Obesity and female sex predominance appear more common in all three conditions.
Visual and vestibulocochlear disturbances (including small-fiber neuropathy) overlap across primary ES, FM, and CFS.
Inferred Conclusions
Moderate or intermittent intracranial hypertension may be a shared pathophysiological mechanism in FM and CFS, potentially causing HPA axis dysfunction via mechanical effects on pituitary blood flow.
The hormonal and clinical similarities between primary ES and FM/CFS suggest that CSF pressure dysregulation warrants investigation as a potential contributor to ME/CFS and fibromyalgia pathogenesis.
Further research specifically examining CSF pressure in FM and CFS populations is needed to test this hypothesis.
Remaining Questions
Does CSF pressure dysregulation directly cause the symptoms and hormone abnormalities in FM and CFS, or is it a secondary effect?
What This Study Does Not Prove
This is a narrative review, not original research, so it does not provide new experimental data or establish causation between CSF pressure and ME/CFS or fibromyalgia symptoms. The review identifies associations and overlapping features but cannot prove that CSF pressure dysregulation is the primary cause rather than a secondary effect or coincidental finding in some patients.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →