Research Digest – September 2014: Cortisol in ME/CFS

Cortisol is a hormone that is produced in the adrenal glands where it enters into the circulation to dampen inflammation. It does this by entering into the cytoplasm of cells, binding to the cortisol receptor (called the glucocorticoid receptor) and then moving into the cell nucleus to bind to DNA and regulate the expression of inflammatory molecules.

Cortisol is an essential hormone for immune function and many studies have shown that cortisol is low in ME/CFS patients – known as hypocortisolism.  Recent articles find increased cortisol receptor expression is associated with post-exertion malaise (PEM), low cortisol is associated with more severe PEM and a return of cortisol to normal levels is associated with recovery.

In this month’s research digest, we review three studies that look at the effect of cortisol on function and post-exertional malaise in ME/CFS.


In a Solve ME/CFS Initiative funded study published in Fatigue: Biomedicine, Health & Behavior Jacob Meyer, a PhD candidate at the University of Wisconsin, worked with a team of investigators from the University of Wisconsin, Madison, Marshfield Clinic Research Foundation and the University of Utah to study gene expression using an exercise challenge.  Thirteen ME/CFS patients and 11 healthy controls had blood samples taken before and after a maximal exercise challenge.  Compared to controls, ME/CFS patients had increased expression of 2 genes – the glucocorticoid receptor and the adrenergic alpha 2a receptor.  This increased gene expression was associated with PEM symptoms.  The authors suggest that these finding, particularly as they relate to cortisol, may lead to an understanding of the biological mechanism of PEM.


A short communication titled “Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome” was published online in the journal Psychoneuroendocrinology.  Daniel L. Hall and Michael Antoni from the Department of Psychology at the University of Miami together with Mary Ann Fletcher and Nancy Klimas from the Institute for Neuro Immune Medicine, Nova Southeastern University found that greater stress management skills was associated with higher cortisol levels upon wakening and less PEM severity.  The investigators recommend that similar research be conducted over longer periods of time to determine if by improving stress management skills, cortisol regulation improves and ME/CFS patients experience less PEM.


In another study published earlier this year in Psychoneuroendocrinology titled “The role of hypocortisolism in chronic fatigue syndrome”, investigators from the Netherlands examined cortisol levels in young ME/CFS patients participating in the FITNET (Fatigue In Teenagers on the interNET) trial.  FITNET, an internet-based cognitive behavioral therapy program for young ME/CFS patients. These investigators found that the cortisol levels in patients that improved after 6 months of treatment returned to normal levels.  ME/CFS patients that did not respond to treatment had slight increases in cortisol levels but still below normal.  The investigators conclude that the return of cortisol levels to normal is associated with treatment success and that poor functioning of the hypothalamic-pituitary-adrenal (HPA) axis that regulates cortisol levels plays a role in ME/CFS symptoms.  Understanding what contributes to HPA axis dysfunction could help improve ME/CFS treatment.