Neuroinflammation and Cortisol Issues

Could Neuroinflammation Be Triggering the Cortisol Issues in ME/CFS and Fibromyalgia? – Health Rising – by Cort Johnson | Jun 18, 2020

More than any other substance, cortisol demonstrates how integral a role the stress response plays in the functioning of our body.

Our main stress hormone, cortisol is best known for the role it plays in jacking up our fight or flight system, but this versatile substance also

  • affects our metabolism,
  • tamps down inflammation,
  • regulates blood pressure,
  • affects glucose levels, and even
  • impacts our sleep/wake cycle.

Too much cortisol can result in

  • anxiety,
  • depression,
  • headaches,
  • memory and concentration problems,
  • digestion issues,
  • heart disease, and
  • trouble sleeping. 

Too little cortisol can result in

  • fatigue,
  • muscle weakness,
  • digestive issues (diarrhea, nausea, vomiting) and
  • low blood pressure and
  • weight loss.

The idea that one-and-done measurements can tell us much have been taking a beating lately.

As it should!

Our bodies are constantly adjusting our inner biochemical balance which shifts constantly in response to our activities: eating, exercising, and sleeping.

Blood tests taken for studies on particular days when our bodies fluctuate so much during every day, cannot capture the “real” level of hormones.

Because cortisol is secreted according to a circadian rhythm, the authors asserted that that rhythm – which is unique to each individual – must be taken into account.

They believe that asking whether we have too much or too little cortisol is much too simple a question for this dynamic hormone.

Here, Cort references three studies on cortisol:

  1. Characterization of Cortisol Dysregulation in Fibromyalgia and Chronic Fatigue Syndromes: A State-Space Approach. Pednekar DD, Amin MR, Fekri Azgomi H, Aschbacher K, Crofford LJ, Faghih RT.IEEE Trans Biomed Eng. 2020 Mar 5. doi: 10.1109/TBME.2020.2978801. Online ahead of print.PMID: 32149617
  2. A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients With Chronic Fatigue. Divesh Deepak Pednekar, Md Rafiul Amin, Hamid Fekri Azgomi, Kirstin Aschbacher, Leslie J Crofford, Rose T Faghih.  Conf Proc IEEE Eng Med Biol SocJul;2019:6896-6901. doi: 10.1109/EMBC.2019.8857427.
  3. Linking Disease Symptoms and Subtypes With Personalized Systems-Based Phenotypes: A Proof of Concept Study“Kirstin Aschbachera,b,* , Emma K. Adamc , Leslie J. Croffordd, Margaret E. Kemenya, Mark A. Demitracke, and Amos Ben-Zvif.  Brain Behav Immun. 2012 October ; 26(7): 1047–1056. doi:10.1016/j.bbi.2012.06.002.

While the daytime cortisol levels were similar to healthy controls, things went a bit haywire during the night. 


Cortisol was not being cleared, or taken up, by FM patients’ cells as quickly as it usually is. That extra supply of cortisol resulted in cortisol being pulsed through the system fewer times and at lower levels than usual compared to the healthy controls.  That was an indication of “blunted feedback signaling”; i.e. cortisol production was not shut down when it should be and tended to go on longer than normal in FM patients.

When hormones like cortisol become overly available like that, the glucocorticoid receptor that usually responds to it may start ignoring it… could explain the blunted inhibitory feedback other studies have found.

If the glucocorticoid receptors on FM patients’ immune cells turn a blind eye to cortisol, they may keep the pro-inflammatory cytokines that produce pain.

One study found evidence of a blunted anti-inflammatory response to exercise.

studies have clearly shown a relationship between balky cortisol production and increased pain sensitivity.

Chronic Fatigue Syndrome (ME/CFS)

ME/CFS patients, on the other hand, had more secretory events than usual, but produced lower levels of cortisol during the early morning hours compared to the healthy controls

A high sensitivity phenotype is not, as one might think, associated with hypercortisolism. Instead, this kind of hyperactivity – which could result from chronic stress – appears to be associated with hypocortisolism, or low cortisol levels.

That authors speculated that that “high sensitivity phenotype” may be helping the ME/CFS/FM patients to counter-balance high levels of neuroinflammation.

Circadian Pattern Lost

Cortisol is produced according to a circadian rhythm.

It hits rock bottom during the early evening – a good time for a stress response hormone to shut down – and then climbs to a peak in the morning.

The study found that a quicker cortisol rebound at night was associated with better sleep in the healthy controls. That pattern, though, was completely missing in the FM and ME/CFS patients

The Other Overactive Stress Response

The authors didn’t offer any treatment options other possibly mineralocorticoids, but are going to add ACTH – the factor responsible for synthesizing cortisol – to their modeling efforts

Way back in 2008, though, a study suggested that intranasal insulin, of all things, was able to reduce hyperactivity of the HPA axis.

This is one of those currently inexplicable oddities that occasionally crop up in medical research.

How it would affect people with ME/CFS – who have increased secretory events, but reduced cortisol production in the early morning hours, or FM patients, with their reduced cortisol clearance – is unclear.


The most comprehensive cortisol study ever in ME/CFS and FM found cortisol abnormalities during the night in ME/CFS but not during the day.

The authors characterized the ME/CFS/FM group as a whole as having a “high sensitivity phenotype”; i.e they either produced cortisol more rapidly (ME/CFS) or produced it for longer periods (FM).

Time will tell how important or not important these findings are but the study does provide more evidence of HPA axis abnormalities in these diseases.

It bears noting that these researchers have twice gone to extraordinary lengths – doing blood draws every ten minutes for 24 hours – to assess cortisol/ACTH levels.

The authors didn’t provide treatment suggestions, but are now going to dig into patterns of the ACTH – the hormone that tells the adrenals to produce cortisol.

3 thoughts on “Neuroinflammation and Cortisol Issues

  1. canarensis

    “intranasal insulin”…whoa. Wha? I skimmed the abstract & didn’t see anything about what prompted them to try that, for this. How the heck did they come up with that idea? One of life’s mysteries, I guess. My pcp that retired a few years ago checked my cortisol levels a few times & they were low…decade or two prior, they were very high…her theory was, my adrenal glands were shot from years of chronic stress. but nobody ever did a time course or tried anything that took circadian rhythms into account. I’m sure the insurance biz would never allow that.

    Interesting post!

    Liked by 1 person


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