Is there such a thing as adrenal fatigue? You may see and hear this term all the time, but it is not actually supported by the current scientific literature. If you perform a Google Scholar search of adrenal fatigue, nothing of any real significance appears. The term has not been recognised by any Endocrinology society and they claim that there is no hard evidence for it’s existence (1). A more accurate term perhaps would be HPA axis dysfunction.

Adrenal Fatigue has been used to describe a condition caused by a long or constantly recurring exposure to stress. The theory states that chronic stress causes a failure of the adrenal glands through overuse. Although this seems an attractive theory, the evidence is not really robust enough to support it. In most of the cases where people are diagnosed or have self-diagnosed with adrenal fatigue, they don’t actually have low cortisol. 

 

Portrait of stressed businessman burnout holding his head with both hands at work

Stress and stress hormones

Cortisol is a stress hormone, released during (but not only) as part of a response to stress. It has evolved with us as a species because it offers an evolutionary advantage. If the stress response was not useful and served no purpose, it would have died out long ago.

In the distant past, if we were being chased by a predator or under attack from a rival tribe, the stress response served us well. It provided that immediate “fight or flight” response to get us ready for action.

  • The heart rate increases.
  • Breathing increases in rate and depth (to supply the body with more oxygen).
  • The body produces more glucose for energy.
  • Muscle tension increases to improve strength and endurance.
  • Blood clotting increases in preparation for possible tissue trauma.

There is also a more delayed release response of cortisol too, which further help you get ready for action and allow the body to continue to stay on high alert.:

  • Glycogen is broken down in the liver to produce more glucose.
  • Arousal and anxiety is increased 

This is all well and good in a life threatening situation. But, this response is not supposed to be activated frequently or for prolonged periods of time. Long term or excessive stress has been associated with:

  • Cardiovascular disease (2),
  • Diabetes (3), (4)
  • Worse sugar control if you are diabetic already,
  • Hypothyroidism and
  • Autoimmune diseases.(5).

 

As with all endocrinology issues, it can get a little complex…

Cortisol is released by the adrenal glands that sit atop the kidneys. But how is it released?

Stress, illness and the time of the day all act on an area of the brain called the hypothalamus. Corticotropin-releasing hormone, CRH, is secreted from the of the hypothalamus and acts on the anterior pituitary gland to release ACTH: adrenocorticotrophic hormone. ACTH is a hormone that stimulates the adrenal glands to release cortisol.; this is the hypothalamic-pituitary-adrenal axis (HPA). The HPA axis is a negative feedback system, where the presence of cortisol inhibits the production of CRH and ACTH.

Hypothalamic-pituitary adrenal axis anatomy

 

Due to the presence of glucocorticoid receptors in almost every cell of the body, cortisol affects the many organ systems described above.

Normal cortisol release is highest just after you wake up and lowest at night, so that you feel tired and go to sleep.

Why it should be called HPA axis dysfunction, not adrenal fatigue

Erroneous understanding of physiology involved is often why people get it wrong. The cortisol often measured in salivary testing is the free-fraction, or unbound to protein carriers. However, free cortisol is only about 3 to 5 percent of the total cortisol in the body at any given time. So therefore, free cortisol, while it is the most potent form, is not the best marker for overall cortisol production. It is possible to have a low free cortisol (hence the idea that your adrenals have fatigued or run out of cortisol) and a high total cortisol.

Yet another reason for the perpetuation of the adrenal fatigue idea is that saliva cortisol testing often returns falsely low values, especially in the morning. Depending on when it is taken, you may miss the cortisol awakening response, which can contribute to about half the 24hr cortisol value estimated by salivary testing. If you miss this, your cortisol levels could come back abnormally low

Something else that contributes to the adrenal fatigue misnomer is the vastly different ranges and measurement units used by labs that perform saliva testing. These differences can be huge. A value that is normal in one lab could be abnormally low In another’s.

An abnormal cortisol release rhythm has been described. So if you measure a salivary or blood cortisol level, depending at what time of day it was taken, it may be low. But you could have an elevated cortisol earlier or later on in the day which means that your total cortisol levels are ok. The abnormal pattern of release of cortisol is often observed in HPA axis dysfunction

All these factors can lead to an over-diagnosis of low cortisol or a flattened cortisol curve. If you look in the scientific literature, you’ll see many studies demonstrating the effects of stress via dysfunction of the HPA axis, but it’s usually cortisol resistance, a high cortisol, or disruption of the diurnal rhythm, that are far more prevalent than low cortisol as a mechanism. However, even if cortisol is low in some patients, it’s rarely due to the adrenals being fatigued or exhausted and unable to produce it. Instead, it is the control mechanisms for cortisol, mostly found in the brain and the central nervous system, as well as in local tissues, that may be causing the problem.

This is why it’s important to see someone who understands all of this.

 

Relax - Stress signpost with forest background

 

Dysfunction of the HPA axis is extremely common in today’s society and modern life almost guarantees HPA axis dysfunction. Most people I know feel overwhelmed by the pace of life and the demands on their time. Many people are working more hours per week and are chronically sleep-deprived. Financial worries, a lack of physical activity, not enough exposure to natural daylight, glycaemic disruption (from a poor diet) and circadian disruption can all upset the normal functioning of the HPA axis. 

HPA axis dysfunction is something everybody should pay attention to. Why? If you are not managing your stress properly, your best laid diet, exercise and health plans go down the drain. One could even say that it is very difficult to successfully manage any chronic health condition without addressing the HPA axis, because of the HPA axis effects on nearly every cell and tissue in the body. It has a particularly strong impact on the immune system, mechanisms that drive inflammation, and glucose regulation. These factors that are involved in most modern, chronic diseases. This explains why stress is linked to a huge number of conditions, ranging from cardiovascular disease, diabetes, infertility and dysmenorrhea, skin conditions, to IBS and IBD, to depression and anxiety, to autoimmune diseases.

However, it is not always easy to address this issue. Addressing HPA axis dysfunction often involves making significant lifestyle changes, which are often far more difficult to implement than switching to a new diet / exercise regime or simply taking some supplements. This is because they require a deep self-examination, with a willingness to scrutinise and challenge some deeply ingrained lifestyle beliefs, habits, and behaviours.

 

References

1). http://www-personal.umich.edu/~nesse/Articles/Stress&Evolution-2000.PDF

2) Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study, Dr Ahmed Tawakol, MD  *et al. Published:January 11, 2017

3) Psychological Stress May Induce Diabetes-Related Autoimmunity in Infancy Anneli Sepa, PhD1, et al Diabetes Care 2005 Feb; 28(2): 290-295.

4) Does Emotional Stress Cause Type 2 Diabetes Mellitus? A Review from the European Depression in Diabetes (EDID) Research Consortium. Published on February 11, 2010. Frans Pouwer

5) Association of Stress-Related Disorders With Subsequent Autoimmune Disease Huan Song, et al JAMA. 2018;319(23):2388-2400