Cortisol levels in ME/CFS

[bobbler]

Throwing this link in here and hoping it is OK to the idea of the thread - although it seems to apply to measurement of hormones beyond just cortisol, I think it is interesting if the way things should be measured is indeed moving on:

Clinical Endocrinology—Time for a Reset?

research-information.bris.ac.uk

Clinical Endocrinology—Time for a Reset?​

Stafford L. Lightman* April 2024

Abstract​

Measurement of blood levels of circulating hormones has always been the cornerstone of the biochemical diagnosis of endocrine diseases, with the objective of detecting hormone excess or insufficiency. Unfortunately, the dynamic nature of hormone secretion means single-point measurements of many hormones often lack diagnostic validity. Endocrinologists have devised complex dynamic tests as indirect assessments of the functioning of the hormone system under investigation. Recent advances in the measurement of dynamic hormone changes across the day now offer an opportunity to reconsider whether there might be better ways both to diagnose and to monitor the therapy of endocrine conditions.

link to paper: https://academic.oup.com/jes/article/8/4/bvae024/7606556


Just scanned so far but there are interesting points that perhaps relate to other threads such as:

1. The first lesson is that if we have wearable sensor technology, we should be able to monitor a patient's hormone levels in their own home/work environment—which is, of course, what we actually want to know.

And the interesting part in the discussion before it (which included the issue of sleep affecting measures, but being something you'd want to measure as part of a cycle) reminded me of the dilemma we have with PEM vs exertion, influences impacting things and 'cycles' that we have with ME/CFS and experiments/tests that themselves involve eg travel or even just additional activity even if it was in the home (which then might necessarily cause compensation/change to other activities in a normal week in response)

 

[Sean]

And not just hormones either, I will bet. Homeostasis is certainly a thing, but it is a dynamic equilibrium on at least many measures (e.g. blood pressure).

When extended real-time collection of what are currently single point data can be done for days-months can be done then a whole new set of patterns and understandings are likely to emerge, and help redefine health and sickness, and how to respond to it.

 

[Suffolkres]

Ah. I had not seen that. I think I now understand your previous comment about the low levels being related by some common artifactual influence. The apparent absence of cortisol in CSF makes no real sense as consequence of depleted CRH cells unless these cases are unusual instances of pre-terminal adrenal failure it seems. I think we need to see detailed published findings.

My husband demonstrated adrenal insufficiency, and did so in 2006 via saliva tests; hypothyroidism from plus 24 hour urinary collection testing. But NHS does not recognise these results done privately.

NHS Synthetic test did not show any abnormality.

Recent Cardioloy reviews also suggest secondary adrenal /thyroid problems as contributory to his symptoms pattern.

 

[forestglip]

This is on chronic fatigue, not ME/CFS, but it still may be interesting:

The association between hair cortisol levels, Epstein-Barr virus infections and chronic fatigue in adolescents, 2026, Kongsnes, Wyller et al

No association of pre-infection hair cortisol with 6 month chronic fatigue:

Preinfection hair cortisol concentration did not predict chronic fatigue six months after acute EBV infection.

Small correlation (R²=0.02) of higher chronic fatigue at 6 months with lower hair cortisol at 6 months:

A trend toward a positive association between preinfection hair cortisol and fatigue during acute infection, became significantly negative six months later.

 

[SNT Gatchaman]

Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME/CFS (2026)

Participants were slightly obese, predominantly women (76%), and with poor subjective health (e.g., mean quality of life 34 ± 14 on a 0-to-100 scale). Routine blood chemistry analyses did not reveal any general deviations from normal, as reflected by cortisol and C-reactive protein (CRP) levels in Table 1.

 

[forestglip]

A review of ME/CFS studies:

Neuroendocrine signature of ME/CFS: Meta-analytic evidence for bioactive cortisol deficit and exaggerated feedback sensitivity, 2026, Woo et al (thread link)

We identified 46 case–control studies (comprising 46 independent datasets, including 12 pharmacological challenge studies), involving 1388 ME/CFS patients (71.9% female; mean age 37.3 ± 6.2 years) and 1349 matched healthy controls.

Meta-analyses showed lower salivary cortisol at awakening and in the morning. Reductions were also observed in 24-h urinary cortisol and hair cortisol. In pharmacological challenge tests, patients exhibited impaired cortisol release in response to adrenocorticotropic hormone (ACTH) stimulation and exaggerated suppression following glucocorticoid administration.

 

[Jonathan Edwards]

A recent talk by Chris Pontng has been posted on the

Genetics: Chromosome 6 BTN2A2 and BTN3A3​

thread. He focuses in on HPA axis. We have already discussed a lot of the issues but I think this new talk provides a very nice focus for where things are at.

 

[SNT Gatchaman]

Analysis Of Salivary Herpesviruses Reveals Associations Between HHV-6 And Long COVID Severity (2026, Preprint)

To capture diurnal dynamics of hormone production, salivary cortisol and testosterone were measured at 4 morning time points (in 15-minute increments from waking), an afternoon time point (8 hours after waking), and an evening time point (16 hours after waking) over two consecutive days using ELISA. […] Cortisol peaked 15-30 minutes after waking and was secreted at similar levels in participants with LC and controls. To quantify total Cortisol Awakening Response (CAR), AUC was measured from waking levels to 45 minutes, and it did not differ between LC and Control. Total cortisol production over the course of the day measured with AUC trended lower in LC than Control but did not reach significance (p= 0.076). Morning and whole day cortisol was not associated with LC status, herpes viral shedding, sex, BMI, hormonal medication use, or time from infection when assessed using a linear model.

there were no significant relationships between salivary cortisol, testosterone or estradiol and LC status or [LC Propensity Score]. Although we observed a trend towards lower whole-day salivary cortisol in those with LC, this was not statistically significant. These observations contrast with previous findings by Klein et al. of lower serum cortisol in people with LC. The discrepancy may be explained by diverences in measurement of free vs. bound hormone between serum and saliva, the viral variant that triggered LC, vaccination status, or by the fact that participants were enrolled ~2 years after their initial infection in this study, a much later time from infection than Klein et al.