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Is the HPA Axis Your Fatigue Trigger?

Jul 8, 2021 | Inflammation & Autoimmune Disease

One of the most devastating side effects of autoimmune disorders is fatigue. A 2015 survey revealed that 98% of autoimmune patients suffer from fatigue and 59% said that it is “probably the most debilitating symptom of having an autoimmune disease”. While inflammation is usually a big reason behind the constant brain fog, there may be something else that is triggering fatigue. It used to be called “adrenal fatigue”, but now it has a more appropriate name: HPA axis dysregulation.

What is the Hypothalamus-Pituitary-Adrenal Axis?

The Hypothalamus-Pituitary-Adrenal (HPA) axis is the major stress responding system in the body. This axis contains the hypothalamus and pituitary gland (which are both situated in the brain), and the adrenal glands (located on top of the kidneys). When the body senses an ongoing stressful event, the following cascade of events occurs:

  • The hypothalamus releases corticotropin-releasing hormones (CRH)
  • CRH triggers the pituitary gland to release adrenocorticotropic hormone (ACTH)
  • ACTH travels down through the bloodstream and stimulates the adrenal glands to release glucocorticoids, or cortisol (1)

Cortisol is a stress hormone. It shifts the body into that “fight or flight” mode to handle the stressful event. This hormone keeps the heart rate and blood pressure elevated, suppresses the immune response, triggers the release of blood glucose to give the cells energy to escape the threat, and keeps blood flowing to the muscles, heart and vital organs that are necessary for survival (2). 

When the stressful event is over, the HPA axis works as a feedback loop to reset the body. High levels of cortisol trigger the hypothalamus and pituitary gland to stop producing CRH and ACTH, which ultimately stops the production of cortisol. The parasympathetic nervous system then kicks in to put the brake on the stress response, and the body returns to normal.

What is HPA Axis Dysfunction

HPA Axis dysfunction or dysregulation occurs when the feedback loop of this system stops working properly. Under chronic stress scenarios, cortisol remains elevated. This keeps the HPA axis turned on. Over time, the three components of this axis become desensitized and are unable to properly produce hormones that both respond and dampen the stress response. This doesn’t only affect the stress hormones though. A number of other hormones and neurotransmitters rely on the HPA axis to function properly, including melatonin, DHEA, epinephrine, insulin, thyroid hormones and sex hormones.

There are several symptoms of HPA axis dysfunction, including:

  • Issues with sleep, especially waking up in the morning.
  • Thyroid issues
  • Weak immune system
  • Fatigue and brain fog
  • Inflammation
  • Issues with blood sugar
  • Low libido
  • Depression and/or anxiety
  • Increase in abdominal fat
  • Inability to handle stressful situations

What is the connection between HPA axis dysregulation and fatigue?

The body’s natural sleep cycle depends on the circadian rhythm. The circadian rhythm is an internal clock that keeps many of our bodily processes in sync. Interestingly enough, it also has a feedback loop located in the hypothalamus and helps regulate the release of glucocorticoids. Sleep quality is also highly dependent on cortisol. Cortisol needs to be released at certain times throughout the day and night to keep the circadian rhythm balanced. Dysregulation in either the HPA axis or the circadian rhythm cycle can lead to elevated cortisol levels. And when cortisol levels are higher than normal, that can affect sleep (3).

Fatigue is also connected to CRH. Researchers have noticed an uptick in fatigue levels in patients who have issues producing CRH. Additionally, this inability to produce enough CRH has been seen in patients dealing with systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), fibromyalgia and chronic fatigue syndrome (CFS) (4). 

How is HPA axis dysregulation diagnosed?

HPA axis dysfunction can be tricky to diagnose. Some practitioners use a 4-point salivary cortisol test. This helps create a picture of daytime cortisol to look for any unusual patterns or spikes. Testing sex hormone levels can also help reveal if anything is out of the ordinary. Typically with HPA axis dysregulation, sex hormone levels will be lower than normal. Looking at lifestyle, stress levels, sleep quality/quantity and symptoms also helps paint a picture of what might be going on. 

Part 2 of this series will investigate lifestyle and nutrition tips to help manage HPA axis dysfunction. Stay tuned!

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