Cortisol levels in ME/CFS

[EndME]

Would that disappoint those 1st responders who only want the stress-response option with a multiple choice MUS question to pass their easy-read neuro-rehab exam for re-enablement of crippled sufferers with medically unexplained, endearing but enduring and persistent symptoms of dysregulating, factitious, false illness-belief, which "we all believe and teach" making it the only realistic and pragmatic opportunity (by proxy)?

I think one also has to admit that this wasn't only a BPS narrative but also a narrative spread by people believing in a "biological basis". For example Putrino and Iwasaki were giving widespread interviews on having found a "biological basis" and biomarkers for Long-Covid on the basis of results that anybody should be able to see couldn't stand the test of time.

 

[Arfmeister]

We can almost close the thread I would have thought! Cortisol is clearly irrelevant.

I definitely wouldn’t close the thread. (But I know you’re not planning to do that )

As I’m busy with analyzing the lowest quality data available : online polls and quantitive patient experiences - with glucocorticoids

• I still haven’t finalized this survey, but I already find it quite interesting
• therefore I’d like to give a snapshot of the data (but mind you it’s still work in progress and there’s a lot of detail I would like to lay out)

It’s not based on supposedly low cortisol in ME/LC - but on a big ME-subgroup that had benefits from supplementing in cortisol

Reason I got interested in glucocorticoids is the remarkable improvement I got on a 4 week course of steroids (best improvement I ever had in 17 years). But always keep in mind, glucocorticoids are nasty drugs with a lot of long-term side effects.

Anyway, here is some preliminary data. When I have more conclusive data, I will post it with a lot more detail.

Overview ME-Patient experiences with:

• Hydrocortisone (cortisol equivalent)
• Prednisone / Prednisolone
• Methylprednisolone
• Dexamethasone
• Betamethasone

 

[Hutan]

Thanks Arfmeister

It’s not based on supposedly low cortisol in ME/LC - but on a big ME-subgroup that had benefits from supplementing in cortisol

I believe that things like prednisone can induce feelings of wellbeing and high energy even in healthy people. So, I think that needs to be kept in mind when evaluating the impact of these drugs on people with ME/CFS. I'm actually surprised that there isn't a higher percentage of people reporting a benefit.

e.g. this abstract from a 1988 study:

It is a clinical impression that some patients given oral corticosteroids develop a sense of wellbeing that is 'inappropriate' to improvements in physical health. This has been termed steroid 'euphoria', but unlike steroid-induced psychosis it has not been documented. To test for the size and frequency of this phenomenon, 20 patients with severe chronic obstructive airways disease (mean FEV1 0.86 l) were given 30 mg of prednisolone for 14 days, after a period of placebo administration in a single-blind study.

Lung spirometry and arterial saturation during exercise were measured serially, together with established measures of mood state. No changes in spirometry or arterial saturation during exercise were detected until 7 days of active therapy. Mood state did not change during the placebo period, but small significant reductions in anxiety and depression were measured after 3 days of prednisolone and before any measurable improvement in lung function. Mood state did not then further improve, despite measurable improvements in lung spirometry.

This is evidence that prednisolone may produce a mild 'inappropriate' sense of wellbeing within a population receiving the drug, rather than as an occasional idiosyncratic response.

 

[Lou B Lou]

Thanks Arfmeister

I believe that things like prednisone can induce feelings of wellbeing and high energy even in healthy people. So, I think that needs to be kept in mind when evaluating the impact of these drugs on people with ME/CFS. I'm actually surprised that there isn't a higher percentage of people reporting a benefit.

e.g. this abstract from a 1988 study:

@Hutan wrote - "I believe that things like prednisone can induce feelings of wellbeing and high energy even in healthy people."

I had a course of high dose Prednisolone from early September. 40mgs for 4 weeks then gradually reduction (still reducing very slowly).

I definitely had the feelings of wellbeing on the higher dose, down to 25mgs, but definitely no increase in energy.

I had my normal ME response to the additional appointments, which was PEM (GP and hospital, travelling, upright in waiting rooms, walking around the hospital, medical investigations that led to the prescribing of prednisolone, the prescribing was nothing to do with ME).

The feelings of wellbeing were not really euphoria, but were quite pleasant and meant I was not as fed up as I probably should have been.

 

[Jonathan Edwards]

Yes, there are various reasons why one would expect steroids to help people feel better, at least short term, but it is crucial to note that this has no bearing on the question as to whether abnormal steroid regulation contributes to ME/CFS symptoms. That link would be non-sequitur.

 

[Arfmeister]

I'm actually surprised that there isn't a higher percentage of people reporting a benefit.

Yes. There’s many patients that had positive effects during steroids, but the negative side effects coming off steroids classified it as negative or even keel. Steroids hangover.

- "I believe that things like prednisone can induce feelings of wellbeing and high energy even in healthy people."

But does euphoria account for:

• increase PEM threshold (from bed/housebound to being temporary very mild)
• lower orthostatic intolerance from first day(s)
• Erase brain fog (e.g bringing old forgotten memories back)
• Or in some cases complete temporary remission

All for the time taking (higher than replacement dosage) steroids* ?

*this is some examples from various good responders

@Hutan What is your experience with steroids, if I may ask?

 

[Lou B Lou]

Yes. There’s many patients that had positive effects during steroids, but the negative side effects coming off steroids classified it as negative or even keel. Steroids hangover.

But does euphoria account for:

• increase PEM threshold (from bed/housebound to being temporary very mild)
• lower orthostatic intolerance from first day(s)
• Erase brain fog (e.g bringing old forgotten memories back)
• Or in some cases complete temporary remission

All for the time taking (higher than replacement dosage) steroids* ?

*this is some examples from various good responders

@Hutan What is your experience with steroids, if I may ask?

The reason I was prescribed prednisolone (and high dose cortisone body cream) had nothing to do with ME, but was for a very recent auto immune disease called Bullous Pemphigoid.
By feelings of wellbeing I mean I felt quite good in my head on the higher doses. But there was no corresponding improvement in the state of my body health or any ME symptoms.


I had no improvement in ME, no improved energy, no increase in PEM threshold, no improved cognitive function, no improvement in OI.

I was (and remain) more ill in ME terms while taking prednisolone, with PEM, needing to be in bed more not less. And still am (am still reducing the medication dose).

I first put that down to having had to attend GP and hospital appointments in September, with travelling, and hours at the hospital having tests and biopsy. Then a week and a half of daily phone calls chasing up my prescriptions as there was a difference of (NHS) opinion as to who was supposed to be doing the prescribing, and the pharmacy got confused between all the various prescriptions. That caused a gap of days with no medication and I had to start the course of prednisolone again. Then there was an arduous daily regime of applying cortisone cream for months.

I'm still more sick in ME terms now than before I started the prednisolone in early September. I don't know if it's the additional disease that's taking it out of me, or the medication, or what.


Edit add
I did notice after reducing the prednisolone to about 25/20 mgs a day, that I was having 2/3/4 days of low mood after reducing. I don't normally suffer with low mood. I worked out it was just the medication reduction and just put up with it until around 4 days after reduction my mood just evened out and I felt fine again.


I do think that Drs should warn patients about that effect from the necessary reduction of prednisolone dosage. As I said, I don't suffer with low mood normally, I worked out it was just the medication reduction, and was able to just ride it out until my mood seemed to even out and I felt fine again. BUT, for patients who do suffer with low mood before taking the medication, the prednisolone reduction effects could be more serious or disturbing.

.

 

[Hutan]

On hydrocortisone treatment, this is a copy of a post I made on another thread:

Thought I'd create a thread for the referenced paper on hydrocortisone treatment in CFS, Low-Dose Hydrocortisone for Treatment of Chronic Fatigue Syndrome - A Randomized Controlled Trial, 1998, McKenzie et al

There were 70 people with CFS assessed in this 1998 study. Average baseline morning cortisol, and cortisol after stimulation with ACTH were completely normal. Positive responses to hydrocortisone treatment were limited to one questionnaire among quite a number, were small and were in line with the positive response that healthy people also experience. The authors (including Wessely) themselves concluded that hydrocortisone treatment caused substantially more harm than benefit, saying

We found that low-dose hydrocortisone treatment has mild side effects (Table 3) and affords minimal therapeutic benefit for CFS

@Hutan What is your experience with steroids, if I may ask?

I can't recall having steroids since developing ME/CFS.

 

[SNT Gatchaman]

Possible Involvement of Hypothalamic Dysfunction in Long COVID Patients Characterized by Delayed Response to Gonadotropin-Releasing Hormone (2026)

Table 2. Basal hormone levels of long COVID patients who underwent pituitary stimulation tests.

Cortisol (µg/dL)
7.5 ± 0.8 (Reference range: 7.1–19.6)

in the present patients with long COVID, the peak ACTH and cortisol responses to CRH and their recovery levels at 120 min were nearly normal, failing to detect clear HPA axis abnormalities. Furthermore, assessment of basal cortisol secretion using 24 h urinary collection (UFC) revealed a nearly normal level of approximately 40 µg/day.

 

[Arfmeister]

Average baseline morning cortisol, and cortisol after stimulation with ACTH were completely normal.

I have been reading some of the S4ME threads on cortisol (a lot !) including the patient trials and I was wondering the following:
In many studies, it appears that in ME cortisol levels are (close to) normal. Although morning cortisol is lower vs healthy controls and overall cortisol levels seems more flattened / blunted over the day.

My thinking : cortisol levels are normal or low for most ME patients. Never or seldom high levels.
In PEM, ME patients are not able to handle any form of physical or neurological stress in a proper way

So is it possible that part of the problem is: that when ME-patients get in a PEM crash they fail to mount a proper cortisol response - so they fail to dampen the crash??

• The HPA axis is not able to increase cortisol during PEM and therefore (neuro)inflammation is not managed properly
• The cortisol production is blunted and insufficient to shut down the inflammation and stress responses
• This could be part of the reason that small immune triggers (bacteria,virus) or exertional triggers produce outsized + prolonged crashes
• If so, this would be caused by UPSTREAM mechanisms - e.g. default neuro-immune signaling, triggering sickness behavior
• So NOT a dysfunctional HPA axis as core default mechanism
• the HPA-axis functions properly (ACTH / Cortisol production) but maybe CRH production/input is too low

@Hutan
Have you ever come across any research publication that measured cortisol (and ACTH) levels during PEM ?
- Would be interesting to know if cortisol was ever measured during PEM (e.g. after a CPET test for example)

My own case:

• My morning cortisol and ACTH was measured before breakfast in serum in a moderate PEM state on 2 different occasions. Values were both at the (very) low end, but still within range.
• During PEM, my body nor my psyche can handle stress well. My body aches, strong headache and brain fog with neural inflammation/microglia as culprits IMO.
• As an example of inflammation during PEM: I have my seboric dermatitis flare up during PEM as ‘proof’ that inflammation is increased
• I have been helped by steroids during a 4 months high dosage protocol: it increased my PEM threshold incredibly (from 1 step/day to 300 steps over a sustained Period) and system wide ME-improvement, which to me can impossibly be described to euphoria
• (OR: dopamine is one of the core issues with (my) ME CFS)
• This is the reason of my special interest in cortisol and steroids - Possibly I’m an outlier a or a sub group