Adrenal & Cortisol Status in Fibromyalgia: Cortisol Receptor Resistance

In addition to lower cortisol levels in the morning and throughout the day [in patients who really need higher levels to support them through their daily stress and pain], Fibromyalgia patients demonstrate decreased cortisol receptor sensitivity. This adds insult to the injury.

To achieve the same cortisol-mediated stress, blood sugar and energy metabolism support, fibromyalgia patients need higher levels of circulating cortisol than average patients. Lower cortisol levels plus compromised cortisol receptor sensitivity accounts for much of the symptom load exhibited by fibromyalgia patients, esp as relates to day-night rhythm problems, increased perceptions of stress and decreased stress tolerance with anxiety during stressful situations.

Yet again, this situation need not be an obstacle to better health. Moderately increasing cortisol levels through micro-dosing with appropriate hormone therapy makes the world of difference with anxiety, sleep and day-to-day function.


Evidence for an association between an enhanced reactivity of interleukin-6 levels and reduced glucocorticoid sensitivity in patients with fibromyalgia.

Reduced and disturbed glucocorticoid sensitivity was observed in fibromyalgia patients. The very interesting observation in this study, in addition to the disturbed cortisol receptor function, that fibromyalgia patient’s ACTH did not increase during pain pressure point threshold testing: cortisol did increase 3 times [from the pain of the test] and IL-6 increased 4 times [an inflammatory hormone that is problematic in FMS].

Glucocorticoid sensitivity in fibromyalgia patients: decreased expression of corticosteroid receptors.

Fibromyalgia patients exhibited changes in glucocorticoid receptor (GR) affinity and disturbances associated with loss of hypothalamic-pituitary-adrenal (HPA) axis resiliency. There is a lower expression of corticosteroid receptors  in FM patients when compared to healthy controls.

Changes in salivary cortisol and corticosteroid receptor-alpha mRNA expression following a 3-week multidisciplinary treatment program in patients with fibromyalgia. 

“…..Increased resiliency and sensitivity of the stress system is probably related to stimulation of Glucocorticoid Receptor-alpha synthesis by the components of the treatment.”     The conclusion of this study is that due to changes in cortisol receptor sensitivity, Fibromyalgia patients improved in many respects, including pain threshold and resilience of the stress system.


Werner Vosloo ND, MHom




Adrenal & Cortisol Status in Fibromyalgia: Not Enough Cortisol

Fibromyalgia is characterized by a lack of energy, drive & motivation and a general lack of “get-up-and-go”. Mornings are pretty bad, you feel more tired than when you went to bed.

Cortisol levels in the mornings and also throughout the rest of the day are much lower than you need to get through the day’s stress, fatigue and pain.

Adrenal dysfunction is strongly responsible for this lack of restorative sleep or not feeling rested in the morning.

Cortisol is a key adrenal hormone that is essential to maintain healthy:

  • Blood glucose levels   
  • Converting fat, protein and carbohydrate to maintain blood sugar  
  • Immune balance and healthy immune responses    
  • Endogenous anti-inflammatory [more allergies and inflammation when cortisol low]  
  • Blood Pressure
  • Heart and blood vessel tone and contraction
  • Central nervous system activation and motivation
  • Healthy and happy optimistic mood  
  • Stress tolerance
  • Sleep and day-night cycles

Just like thyroid hormone, it is very safe and easy to correct low cortisol levels.

Evaluation consists of symptomatic evaluation and laboratory investigation of cortisol levels at 4 different times of the day, or total cortisol production for a whole day.


Studies to read:

Comparison of the cortisol awakening response in women with shoulder and neck pain and women with fibromyalgia.

Fibromyalgia patients have lower cortisol levels than woman with shoulder and neck pain. Fibromyalgia patients have more symptom burden: pain levels, sleeping problems, perceived stress, and psychological problems related to their condition.


Fibromyalgia syndrome is associated with low cortisol.

Fibromyalgia patients had significantly lower cortisol levels during the day, most pronounced in the morning . As expected, Fibromyalgia patients reported more pain, stress, sleeping problems, anxiety, and depression.

This confirms dysfunction in the hypothalamus-pituitary-adrenal axis in Fibromyalgia patients, with generally lower cortisol values, most pronounced upon awakening.


Delineating Psychological and Biomedical Profiles in a Heterogeneous Fibromyalgia Population Using Cluster Analysis 

An analysis of various subgroups of Fibromyalgia patients indicated that the more symptomatic patients with more severe pain and disability had the lowest levels of cortisol.

Childhood abuse and family dysfunction is reported in 64% of fibromyalgia cases.

When present in the history, there was a greater tendency to a flattened day-night cortisol curve with lower cortisol production.


Werner Vosloo ND MHom


Thyroid dysfunction in Fibromyalgia 3 Mercury and other toxins inhibit conversion of T4 to T3

3. Mercury, cadmium, inflammation, stress, nutrient deficiencies and infections affect thyroid metabolism adversely, even if your thyroid gland is producing a normal and healthy amount of thyroid hormone.

T4 is the main product of the thyroid gland, with deiodinase enzymes in the liver, kidneys, brain and other organs changing T4 into the metabolically active T3. Most [>95%] PCP’s and endocrinologists do not test for free T3, free T4 and the ratio to reverse T3. Reverse T 3 acts as an anti thyroid, slowing metabolism and contributing to fatigue, pain and disease symptoms.

Action item: Don’t settle for just TSH and fT4 as the only thyroid tests ordered for you. Be pro-active and test your fT3 and reverse T3 to assess all of the important thyroid hormones, which enables your integrated, open minded doctor to adjust your thyroid hormones based on your metabolism and enzyme system function.

Next, test for the toxins known that affect deiodinase enzyme function adversely. We know how to remove these toxins safely, but you will only make this an action item if you test for it.



Effects of low mercury vapour exposure on the thyroid function in chloralkali workers.

Reverse triiodothyronine (rT3) was statistically significantly higher in the mercury exposed subjects, with the free thyroxine (T4)/free T3 ratio also higher in the highest mercury exposed subgroups compared with controls.

Thyroid hormones and methylmercury toxicity.

High exposures to the organometal, methylmercury (MeHg), may perturb neurodevelopmental processes by selectively affecting thyroid hormone homeostasis and function.

Removal of dental amalgam decreases anti-TPO and anti-Tg autoantibodies in patients with autoimmune thyroiditis.

Removal of mercury-containing dental amalgam in patients with mercury hypersensitivity may contribute to successful treatment of autoimmune thyroiditis.

Effects of perinatal exposure to low doses of cadmium or methylmercury on thyroid hormone metabolism.

Thyroid hormone metabolism in fetuses and neonates might be a potential target of Cd and MeHg.


Thyroid dysfunction in Fibromyalgia 2 Central Regulatory Dysfunction – unreliable TSH

2. Hypothalamic Regulatory Dysfunction or control center dysfunction is a very prevalent factor in thyroid dysfunction seen in fibromyalgia syndrome.

Control center inadequacy in regulating normal release of TSH and basal lowered fT3 levels are a strong cumbersome problem in fibromyalgia. Typically all lab parameters are low normal, with normal levels of TSH and lower levels of fT4 and fT3.

Fibromyalgia patients respond really well to microdoses of T3 therapy clinically. We accompany T3 therapy with cortisol levels to ensure a satisfactory response.

Action item: Get your TSH, fT4, fT3 levels tested to ensure adequate T3 levels to stimulate metabolism and energy production.



Thyroid function in patients with fibromyalgia syndrome.

Patients with fibromyalgia has significantly lower secretion of thyrotropin and thyroid hormones in response to TRH test.

Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism.

TSH is a poor measure for estimating the clinical and metabolic severity of primary overt thyroid failure. This is in sharp contrast to the high diagnostic accuracy of TSH measurement for early diagnosis of hypothyroidism.

There is no correlation between the different parameters of target tissues and serum TSH.

Neuroendocrine and hormonal perturbations and relations to the serotonergic system in fibromyalgia patients.

The degree to which TSH can be stimulated is decreased in fibromyalgia patients.

Lowered basal values of  free triiodothyronine (fT3) was found in fibromyalgia patients.


Genetic Changes and CFS: Identifying the Culprit – cortisol regulation problems, methylation defects

Genetic Changes and CFS: Identifying the Culprit – cortisol regulation problems, methylation defects

Cortisol regulation problems, methylation of DNA determining functional expression

This study confirms a lot of what we know clinically about the symptom expression pattern and aggravating factors in ME/Chronic Fatigue Syndrome.

This study highlights the importance of the hypothalamic-pituitary-adrenal control axis, but really the hypothalamic-pituitary-endocrine axis in Chronic Fatigue Syndrome/ME, and how the epigenetics [environmental factors] interact with DNA to determine how our genes are expressed.

Methylation of genes [the function of Vit B12, B6, l-methylfolate, TMG/Betaine, DIM etc.] determines how DNA is translated into health or disease.

One of the problems in objectively diagnosing CFIDS/ME, Fibromyalgia, Lyme disease, MS etc is that we lack reliable biomarkers AND that the known biomarkers are characteristic for many of these named conditions – thus pointing us in the right direction but not being very specific.

Currently we combine a symptomatic analysis of symptoms [see adrenal section of the clinic intake form, page 3] with pituitary trophic hormones and also the adrenal production of cortisol measured [saliva] at 4 different times of the day.

This system is rather accurate and is able to help most patients with CFIDS to a healthier, more stable place. This is measured through quality of life and sense of well being increase over net reduction in symptoms.

W.Vosloo ND MHom.


Genetic Changes and CFS: Identifying the Culprit

Contrary to what some might think, our fate is not set upon conception when the genome is created, nor is our fate determined entirely upon the environment into which we are born and live. Instead, everything we are and everything we will be stems from a complex interaction between our genes and our environment, with the environment influencing which genes turn on and off and when, and our genes influence how we react to the environment.

For decades, scientists believed that while the genome was very plastic and could adapt to the environment in very early life, that window closed as we developed in utero. They also believed that genetic changes could only occur through changes to the underlying DNA. Today, however, an exciting new field called epigenetics has set that thinking on its head and created new possibilities for understanding how diseases develop — and how to prevent and treatment them.

Epigenetics refers to patterns of change in gene expression — not the gene itself — that occur in response to such things as nutrition, infection and physical and mental trauma, not genetic factors. These outside influences trigger a process called methylation that affects gene function but doesn’t change the underlying DNA structure.

“Epigenetics is really a funnel by which the outside environment interacts with the genome,” explains CFIDS Association grantee Patrick O. McGowan, Ph.D., assistant professor in the department of biological sciences at the University of Toronto in Canada. This, in turn, influences how cells work (or don’t work). Already, research shows that epigenetic changes are implicated in numerous diseases, including cancer, asthma and heart disease.

And, if Dr. McGowan is right, they may also play a role in the development of chronic fatigue syndrome (CFS).

Disrupted Signaling in Body’s “Conductor”

To understand where Dr. McGowan and his team hope to go with their research, you first need to understand the hypothalamic-pituitaryadrenal (HPA) axis, often referred to as the “conductor” of our body and its responses.


Dr. McGowan and colleagues at the University of Toronto’s Laboratory for Epigenetic Neuroscience

The HPA is one of the most important communication pathways in the brain. The signals it produces (from hypothalamus to pituitary gland to the adrenal glands and back again) help maintain balance in the neuroendocrine system, which enables communication between various hormones throughout your body and your brain; and the sympathetic nervous system, which regulates the infamous “fight-or-flight” system and determines how the immune system responds to environmental stressors.

This latter component involves cortisol, a glucocorticoid hormone that helps dampen immune system inflammation and keep the body in balance. It also “turns on,” or activates, glucocorticoid receptors that then act on hundreds of genes that control development, metabolism, cognition and inflammation. Think of these receptors as a lock, and cortisol as the “key” that unlocks them to allow the hormone to enter the cell and tell it what to do. Yet one of the most consistent findings in CFS is that patients don’t produce enough cortisol. Without that cortisol, immune system cells called lymphocytes continue to release pro-inflammatory cytokines, keeping the system activated and wreaking all sorts of havoc throughout the body. The whole process likely contributes to many of the symptoms of CFS.

If Dr. McGowan is correct, epigenetic changes may be at the heart of this cortisol/cytokine imbalance.

Dr. McGowan’s research has three main goals:

  • Confirm that there is, indeed, altered sensitivity to glucocorticoids and increased inflammatory cytokine production in immune system cells of people with CFS.
  • Identify patterns of DNA methylation and the specific epigenetic locations in the genome in people with CFS.
  • Analyze the epigenomic and genetic changes in CFS patients in conjunction with symptoms, their severity and medication response — all areas associated with the HPA axis.

To do this, Dr. McGowan and his team will use immune system cells from the SolveCFS BioBank. They will first stimulate the cells with a synthetic glucocorticoid hormone to assess their sensitivity to glucocorticoids and cytokine production. They will also extract DNA from the blood cells to evaluate epigenetic patterns and compare the results to those of cells from people without CFS. They also want to see if cells from different CFS patients respond differently, which would provide evidence of subtypes of CFS, something many researchers suspect exist.

“The exciting thing is that we’re looking across the entire genome, so we’re not making assumptions about what system is influencing the HPA abnormalities,” he says.

In addition to identifying potential epigenetic changes, Dr. McGowan and his team will also try to understand the environmental triggers that likely set about those changes. To do this, they will use disease-specific family history and current health reports for the patients whose cells they are examining.

Unlike genetic differences, which are fixed from conception and remain relatively stable across the lifespan, epigenetic differences are stable but respond to environmental factors; thus, Dr. McGowan said, they may be amenable to therapeutic intervention. For instance, some cancer drugs alter gene expression through epigenetic changes. But there are also potential lifestyle interventions that could have similar results, he said.

“I’m really excited about this grant because we are right at the beginning stages of being able to look at very complex diseases like CFS in a holistic way” by targeting the genome, he said. “If we can start to get biomarkers for this disease that correlate with clusters of symptoms, we will have a better idea of how to approach interventions.” Those biomarkers could also make it easier to study CFS, even aiding in early diagnosis of the disease and, possibly, approaches designed to prevent its development in susceptible individuals, as well as targets for treatment.

Learn more about epigenetics with this primer from The Scientist magazine:

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