Many people have high total cortisol when experiencing what has commonly been called adrenal fatigue. The term HPA axis (hypothalamus, pituitary, adrenal) dysfunction or maladaptation is a more accurate description due to the complex interdependence of glands, cells, and the brain. Furthermore, research and statistics show it is usually not a case of low output by the adrenals at all.

Why is this important to understand?

Cortisol has an impact on inflammatory response, thyroid function, glucose levels, and the list goes on.  Studies show that early life events can set up a life long pattern that affects the HPA Axis and cortisol production.  This maladaptation also can occur when there is decreased output by the pituitary gland.  Receptor sensitivity is yet another way in which cortisol signaling can get disrupted. Lastly, reduced bioavailability can happen at the tissue level by way of the binding globulin in the blood, conversion of cortisol to cortisone or cellular transcription.  The point is that the HPA axis is much more nuanced than the concept of adrenal fatigue lets on.

Research and Testing

Much of the research on cortisol has been done based on saliva tests which only show free cortisol.  Free cortisol levels can be very different, even opposite from total cortisol. Improper treatment can easily result.  Looking more closely can lead to early detection of thyroid disease, diabetes, leptin resistance, and even certain cancers.

Pregnenolone and DHEA

Chronic stress leads to lowered DHEA, an important steroid hormone.  There is a common misconception that this is because cortisol is stealing from the precursor pregnenolone. Physiologically there is no evidence of this. Both pregnenolone and DHEA are produced in mitochondria but in different tissues.  Cortisol is actually regulated outside of the adrenals. Also, the amount of cortisol produced is significantly more than DHEA.  Location and function both debunk the myth that stress hormones ‘steal’ from sex hormones.   This is news to me as and not commonly understood in the medical community.   One way that this new theory can be proven is by looking at how supplementing pregnenolone will have no effect on DHEA.

Three ways of looking at Cortisol

  1. Is total cortisol low or high?  Looking into other factors that are present and that will be influenced by this.  Leptin and insulin resistance can be involved.
  2. Is there a disrupted diurnal rhythm?  It is important testing is done properly because the morning cortisol curve happens in the first hour of waking.   Some tests are not specific enough by leaving a window of two hours. This creates misleading results.
  3. Is there impaired cortisol metabolism?  When there is more cortisone present this could indicate thyroid involvement.

In Functional Medicine, we are always seeking underlying cause and looking at the latest peer-reviewed medical research to further preventative medicine.


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