Somewhere In Between: Adrenal Fatigue

As an MD and fellowship-trained Integrative Physician, I am often asked about “health conditions” that are not recognized by the medical community and do not qualify as medical diagnoses for a number of reasons: (a) there may be an evolving theory that has not been thoroughly researched, and/or (b) there may be an oversimplified physiologic process or finding that, while having some science, lacks consistent connections to the disease process or outcomes. Some theories, when fully investigated, may in time come to be recognized while others will not – the scientific method is a lengthy process. When approached with these “conditions,” I often find myself “somewhere in between” and I continually pour over new research outcomes in an effort to treat patients who are feeling unwell. While I am sympathetic to those who are frustrated with the pace of medicine and the lack of answers pertaining to their health, we must remember that little truths that are strung together produce interesting headlines, but do not make for sound medical practices. This is the second in a three-part series. 

Adrenal Fatigue

Adrenal Fatigue” is an unfortunate term used by some practitioners that has almost nothing to do with the adrenal gland but pertains more to our stress response system, primarily the Hypothalamus-Pituitary-Adrenal (HPA) axis. Inaccurate and oversimplified terms such as “adrenal fatigue,” “adrenal exhaustion” and “adrenal phase” deter many from legitimate underlying issues, most notably chronic stress. Unfortunately, many integrative, functional and alternative practitioners have a poor understanding of the HPA axis and this seems to go unchecked – and is even propagated – by inaccurate teaching. 

What We Do Know 

There is a vast amount of research on stress, the HPA axis and how this influences health and disease. Most stems from the work of endocrinologist Hans Selye and started to show up in the medical literature in the 1930s. Fortunately, this research field continues to grow rapidly and now incorporates the influence of circadian rhythm.  

In terms of health, the stress response prioritizes immediate need, often at the expense of long term health, and this chronic stress has been linked to various diseases and is being studied in many different areas of medicine.  

Most of the dysfunction in this system has to do with feedback mechanisms or signaling pathways to and from the brain, and while the adrenals get all of the attention, it is really the hypothalamus in the brain that is the controller and where problems tend to reside. If we are exposed to stress on a chronic basis for long enough, some of the areas in the brain can become permanently altered.  

What We Don’t Know 

While chronic stress has been implicated as a causal or exacerbating factor to many diseases, what we don’t know in turn is how much of an impact disease plays into further changes in HPA axis dysfunction. As an example, it is not unusual to see very low DHEA levels (dehydroepiandrosterone, a hormone produced by the body’s adrenal glands) in those with autoimmune conditions such as Rheumatoid Arthritis. However, is this a cause or an effect of the disease? 

We currently don’t have well-established reference ranges for age and sex of adrenal hormones.  Many of these hormones can vary greatly at times, such as in puberty and other times of transition and with many hormones there is a natural decline with age. In fact, I personally wonder if the “normal” population may have shifted with an increase in constant stressful stimulus. 

How are these hormones impacted by genetics, prenatal and early life stress or trauma, and how much correction can be expected? Early-life trauma, even that in utero, can have long-lasting effects on HPA axis functioning and responsivity. 

What We Can Do 

Recognize the role of chronic stress in our daily lives and address factors which are modifiable, such as sleep, diet and exercise.  I have seen advice for those with “adrenal fatigue” to abstain from or limit exercise and I do not agree with this.  Regular exercise (as long as it’s not extreme) has been shown to strengthen resilience and is probably one of the best things we can do for our health.  


Accurate and Appropriate Medical Terms

It is important that we use accurate and appropriate medical terms. When we use incorrect and inaccurate terminology it does little to help patients understand their physiology and the relationship between stress and disease. It also tends to widen the gap between conventional and nonconventional practitioners. When we use appropriate descriptive terms we can enhance the credibility of this phenomenon and begin to address complexity.  

Appropriate Testing 

Currently there is a need for more precise, consistent and reliable testing. Much of the testing offered should be updated and reported in consistent ways. I have been disappointed with many of the available testing options, as they tend to use inaccurate terminology and often don’t take into account elements such as light exposure, activity and often fail to capture the cortisol awakening response. Over the years I have developed a more common sense approach and discovered with good history and diagnostic skills testing is often not necessary and with few exceptions rarely impacts therapeutic decisions. 

The bottom line regarding “adrenal fatigue” is that it is an inaccurate label for a complicated medical topic and its lack of understanding is doing a disservice to those who suffer from HPA axis disorders. 

Use of Adaptogens 

Adaptogens refer to botanicals that have the ability to increase non-specific resistance to stress and is a term coined by a Russian physician. There was great interest and research with adaptogen herbs in Russia, and they were even used by athletes and astronauts. As a physician and herbalist, I often use adaptogens such as Eleuthero, Schisandra, Ashwagandha, Ginseng and – my personal favorite – Rhodiola, as they have multiple mechanisms of action and tend to be gentle. We actually do not have a conventional medicine equivalent.  


Despite the vast literature on adaptogens it is still not exactly clear how they work. They tend to have modulating effects, which may reduce stress-induced damage providing anti-fatigue, anti-infectious, antidepressant and restorative properties. Most adaptogens have a good safety profile but can have the ability to interfere with medications, and thus it is best to consult with a knowledgeable physician before taking them.  

Lastly, please avoid or use caution with: 

  • Glandular adrenal products (ground-up adrenals of animals), which can contain adrenal hormones and are sold over the counter. As most of the issues of the HPA axis lie outside of the adrenal gland, there is really no need to take these products.  
  • Over the counter DHEA and Pregnenolone supplements.

We are currently lacking good references for age and sex matched optimal levels of these hormones. We know levels can vary widely in the young and adolescents and typically decline with age. While supplemental DHEA has been studied extensively, results have been disappointing, especially in those with low DHEA, such as patients with autoimmune disorders such as SLE (Systemic Lupus Erythematosus), inflammatory bowel disease and Rheumatoid arthritis. DHEA therapy should be monitored regularly and overseen by a medical practitioner.   There is very little research evaluating the use of pregnenolone, and we know the notion of “pregnenolone steal” is incorrect. While it is probably safe to take a low dose of pregnenolone, there is little information to recommend for or against it at this time.  

The bottom line regarding “adrenal fatigue” is that it is an inaccurate label for a complicated medical topic and its lack of understanding is doing a disservice to those who suffer from HPA axis disorders. 

Worth Reading

Androulakis, Ioannis P., Rao, Rohit, The physiological significance of the circadian dynamics of the HPA axis: Interplay between circadian rhythms, allostasis and stress resilience, ScienceDirect/2019

Cadegiani, Flavio A., Kater, Claudio E., Adrenal fatigue does not exist: a systematic review, NCBI/2016