Trial Report Lower hair cortisol concentration in adolescent and young adult patients with ME/CFS & Q-Fever Fatigue Syndrome compared to controls,'24,Vroegindeweij

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https://www.sciencedirect.com/science/article/pii/S0306453024001616

Anouk Vroegindeweij, Niels Eijkelkamp, Sjoerd A.A. van den Berg, Elise M. van de Putte, Nico M. Wulffraat, Joost F. Swart and Sanne L. Nijhof, Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls, Psychoneuroendocrinology, (2024) doi:https://doi.org/10.1016/j.psyneuen.2024.10711

Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls

Anouk Vroegindeweij a b, Niels Eijkelkamp c, Sjoerd A.A. van den Berg d e, Elise M. van de Putte b, Nico M. Wulffraat a, Joost F. Swart a f 1, Sanne L. Nijhof b

1 a Department of Paediatric Rheumatology/Immunology and Infectious Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands b Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands c Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands d Department of Clinical Chemistry, Erasmus Medical Center, University Medical Centre Rotterdam, the Netherlands e Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, 3015 GD Rotterdam, the Netherlands f Faculty of Medicine, Utrecht University, Utrecht, the Netherlands

Received 19 April 2024, Revised 10 June 2024, Accepted 27 June 2024, Available online 28 June 2024.

What do these dates mean?

Show less Add to Mendeley Share Cite https://doi.org/10.1016/j.psyneuen.2024.107117 Get rights and content Under a Creative Commons license open access Highlights • Hair cortisol concentration (HCC) was lower in patients with ME/CFS and QFS;

• Overall, HCC had a negative association with chronic fatigue syndrome symptoms;

• Except in patients with QFS, in which HCC increased with the presence of symptoms;

• HCC increased significantly during the RCT, regardless of fatigue improvement.

Abstract

Background

In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA).

Methods

Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses.

Results

The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; β=-0.018, p=.035), except in the QFS group (β=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658).

Conclusion

Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

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[Hutan]

The aetiology and pathophysiology of ME/CFS is largely unknown even though several theories have been developed (Afari and Buchwald, 2003, Hwang et al., 2023, Noor et al., 2021, Varesi et al., 2021, Walitt et al., 2024, Tomas et al., 2013, Deumer et al., 2021, Armstrong et al., 2014).

Damn, Walitt and effort preference is cited.

Hypofunction of the HPA-axis has frequently been observed in patients with ME/CFS through low cortisol concentrations in blood, urine, and particularly the salivary cortisol awakening response (CAR) when compared to controls (Tomas et al., 2013, Powell et al., 2013, Tak et al., 2011, Papadopoulos and Cleare, 2012, Nijhof et al., 2014). Research has linked more pronounced hypofunction to increased symptom severity (Tomas et al., 2013, Papadopoulos and Cleare, 2012, Torres‐Harding et al., 2008), identified moderating factors that lower cortisol concentration (i.e., female sex, early-life stressors, low activity levels, sleep disturbances, depression) (Papadopoulos and Cleare, 2012), and studied the use of hydrocortisone as pharmacological treatment of ME/CFS (Toogood et al., 2021). These studies focused mostly on adult patients. Only one study has investigated cortisol in a large sample of adolescent patients with ME/CFS (Nijhof et al., 2014). This study replicated low cortisol concentration in the salivary CAR, and it observed a normalization of cortisol concentration after psychological therapy successfully alleviated disease burden (Nijhof et al., 2014). In contrast to one adult study (Roberts et al., 2010), the adolescent study did not show that lower pre-treatment cortisol concentration predicted poorer therapy response (Nijhof et al., 2014).

Ugh. Actually most people with ME/CFS have been found to have cortisol levels within normal ranges. We know that people who do a lot of intensive physical activity tend to have higher cortisol. Samples of people with ME/CFS don't tend to include people doing intensive physical activity, so the means tend to be lower than in samples of healthy controls We know that different awakening times can affect recorded cortisol awakening response.

We've seen increasing cortisol levels recorded as a result of therapy presented as a supposedly good thing before. Actually, it's probably partly due to people with the most restricted physical activity (and lowest cortisol) dropping out of these studies, and partly due to people increasing their activity (and so increasing their cortisol). In many circumstances, a higher cortisol is taken to be a diagnosis of higher stress, and this is extremely likely in this case.

Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658).

 

[Hutan]

To our knowledge, three studies have been conducted on HCC in ME/CFS. One study found a trend for lower HCC in adult females with ME/CFS when compared to female controls (Roerink et al., 2018). The second study observed similar levels in adults with ME/CFS when compared to adults with atypical depression and to controls (Herane-Vives et al., 2020). The third study pooled women with a diagnosis of ME/CFS, fibromyalgia, or irritable bowel syndrome together, and found that their HCC was higher compared to women with a somatic symptom disorder and equal to controls (Fischer et al., 2022). Clearly, more research is needed to determine HCC status in ME/CFS. This will be the first study to focus on HCC in adolescent and young adult patients.

So, they say one study found "a trend" for ME/CFS hair cortisol to be lower, one found no difference, and another also found no difference. But, people are so convinced that ME/CFS is a reaction to stress, so surely cortisol must be pathologically abnormal. So, they keep looking.

edited to note that the "positive" study is only reported to have found a trend, which is not a statistically valid difference.

 

[Hutan]

Fatigue was labeled as severe with a total score of >39 in patients with ME/CFS, QFS, and PCC, and a total score of >34 in patients with JIA. Previous research has indicated that fatigue severity is perceived similarly between patients with chronic fatigue syndromes and rheumatic conditions using these cut-offs (Worm-Smeitink et al., 2017, Hewlett et al., 2011).

That's the four cohorts - ME/CFS, QFS, Post-Covid Condition and Juvenile Idiopathic Arthritis
Note the cutoffs used for fatigue severity. A level of 34 or more is taken to be severe when someone with Juvenile Idiopathic Arthritis reports it. But when people with ME/CFS and the like report a 34 on the same scale, that isn't severe. They have to report at least 39 to be regarded as severe, because, you know, those chronic fatigue people are always whining and making things out to be worse than they really are...

That's amazing. If you said that about any ethnic group, that they were not credible witnesses to their own suffering, and that the threshold for them to be regarded as having a severe symptom has to be higher than for 'normal' people, I reckon that you could be taken to court.

 

[rvallee]

What kind of weird ass-study is that? Mixing an observational study of a hormone with some random bunch of "strategies", which is not a proper use of the word anyway. There's nothing strategic about randomly trying stuff. Good grief this is pathetic.

 

[ME/CFS Skeptic]

These seem to be the main results:


So the (small) ME/CFS group had lower hair cortisol than the healthy and arthritis but pervious studies have not found consistent results. The authors write:

To our knowledge, three studies have been conducted on HCC in ME/CFS. One study found a trend for lower HCC in adult females with ME/CFS when compared to female controls (Roerink et al., 2018). The second study observed similar levels in adults with ME/CFS when compared to adults with atypical depression and to controls (Herane-Vives et al., 2020). The third study pooled women with a diagnosis of ME/CFS, fibromyalgia, or irritable bowel syndrome together, and found that their HCC was higher compared to women with a somatic symptom disorder and equal to controls (Fischer et al., 2022).

 

[Hutan]

So the (small) ME/CFS group had lower hair cortisol than the healthy and arthritis but pervious studies have not found consistent results.

Yes, and look at the overlap of that small sample with the controls. It is not looking like part of the disease mechanism. At best there might be some downstream impacts e.g. not undertaking strenuous exercise means the body has no need to make high levels of cortisol.