The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure

Abstract

The etiopathogenesis of fibromyalgia (FM) and chronic fatigue syndrome (CFS) is not yet elucidated. Hypothalamo-pituitary-adrenal (HPA) axis dysfunction is reflected in the hormonal disturbances found in FM and CFS. Some study groups have introduced a novel hypothesis that moderate or intermittent intracranial hypertension may be involved in the etiopathogenesis of FM and CFS. In these conditions, hormonal disturbances may be caused by the mechanical effect of increased cerebrospinal fluid pressure, which hampers blood flow in the pituitary gland. Severe intracranial pressure may compress the pituitary gland, resulting in primary empty sella (ES), potentially leading to pituitary hormone deficiencies. The aim of this narrative review was to explore whether similar hormonal changes and symptoms exist between primary ES and FM or CFS and to link them to cerebrospinal fluid pressure dysregulation. A thorough search of the PubMed and Web of Science databases and the reference lists of the included studies revealed that several clinical characteristics were more prevalent in primary ES, FM or CFS patients than in controls, including increased cerebrospinal fluid pressure, obesity, female sex, headaches and migraine, fatigue, visual disturbances (visual acuity and eye motility abnormalities), vestibulocochlear disturbances (vertigo and neurosensorial hearing loss), and bodily pain (radicular pain and small-fiber neuropathy). Furthermore, challenge tests of the pituitary gland showed similar abnormalities in all three conditions: blunted adrenocorticotropic hormone, cortisol, growth hormone, luteinizing hormone, and thyroid stimulating hormone responses and an increased prolactin response. The findings of this narrative review provide further support for the hypothesis that moderately or intermittently increased cerebrospinal fluid pressure is involved in the pathogenesis of FM and CFS and should stimulate further research into the etiopathogenesis of these conditions.

The relationship between serum leptin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels and clinical parameters in primary fibromyalgia patients

“…In our study, we measured serum leptin, IGF-1, and IGFBP-3 levels in patients with FMS and evaluated their relationship with clinical parameters. The results of the studies which show that changes in serum IGF-1 levels play a role in FMS physiopathogenesis are inconsistent 5 , 6 , 9 , 12 , 15 – 20 .…”

“…Lack of GH secretion may also cause muscle microtrauma and/or distortion in the recovery of microtrauma in normal processes in patients at the same time. Many FMS patients have low serum GH levels, with a hypothesized etiology of dysregulated GH/IGF-I axis and in the sympathetic stress axis as well 17 , 18 . In another study, they were reported that the pituitary function was normal in fibromyalgia and the changes in the hypothalamus-GH-IGF-1 axis were largely due to hypothalamic origin and that GH cure should be recommended accordingly in future studies 20 .…”

“…Leptin secretion is inhibited by the sympathetic nervous system while activated by the HPA system 8 , 9 . In recent years, the possible role of leptin in the etiology and pathogenesis of fibromyalgia has been suggested in some studies, but the results are conflicting 6 – 14 . Finding out the causes of symptoms can play a key role in the treatment of fibromyalgia.…”