Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways

  title={Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways},
  author={Gerwyn Morris and George Anderson and Michael Maes},
  journal={Molecular Neurobiology},
There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis… 

Hypothalamic-Pituitary-Adrenal (HPA) Axis and Chronic Fatigue Syndrome in Older Adults: The Rehabilitation Perspectives

With proper coaching and regular facilitation regarding AS, activity participation in older adults with CFS can be greatly enhanced, and Behavioral intervention, such as AS, can supplement therapeutic treatment or may lead to decline in CFS symptoms.

Hypothalamic-Pituitary autoimmunity and related impairment of hormone secretions in chronic fatigue syndrome.

Both AHA and/or APA at high titers associated with hypothalamic/pituitary dysfunction suggest that hypothalamic or pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome

It is concluded that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.

Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?

It is shown how the immune and metabolic abnormalities of chronic fatigue syndrome can be explained by endotoxin tolerance, thus completing the model.

Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability?

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Cancer-Related Fatigue (CRF) are syndromes with considerable overlap with respect to symptoms. There have been many studies that have

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

It is proposed that stimulation of hypothalamic mast cells by environmental, neuroimmune, pathogenic and stress triggers activates microglia, leading to focal inflammation in the brain and disturbed homeostasis, which could be targeted for the development of novel effective treatments.

An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome

It is suggested that ADX is a possible method for establishing a mouse model of CFS reflecting clinical features, especially in neuroendocrine system, along with bilateral adrenalectomy (ADX) as another possible model.

Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

This paper summarizes and expands on the previous publications about the relevance of findings from critical illness for ME/CFS and describes interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses.



Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome

There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and

Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics

There are neuroimmune similarities between MS and ME/CFS, which further substantiates the view that ME /CFS is a neuroimmune illness and that patients with MS are immunologically primed to develop symptoms of ME/ CFS.

Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder.

The results show that lowered levels of CoQ10 play a role in the pathophysiology of Myalgic encephalomyelitis/chronic fatigue syndrome and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by Coq10 depletion, and that patients with ME/CFS should be regarded as a relative contraindication for treatment with statins without Co Q10 supplementation.

Glucocorticoids, cytokines and brain abnormalities in depression

The HPA axis and the genesis of chronic fatigue syndrome

  • A. Cleare
  • Psychology
    Trends in Endocrinology & Metabolism
  • 2004

Neuroendocrine Manifestations in Sjögren's Syndrome: Relation to the Neurobiology of Stress

The data suggest a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid; it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones.

Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways

The model proposed by Harvey and Wessely, which is the rationale for behaviourally oriented interventions, is reviewed, and a bio(psychosocial) model based upon IO&NS abnormalities is likely more appropriate to this complex disorder.