Adrenal Fatigue, HPA Axis Dysfunction, and the Toll That Hidden Stress Can Take on Your Body

by Dr. Susan Tanner, MD

We have discussed the term “adrenal fatigue” in previous newsletters, and why its symptoms occur often in mold-injured patients. The term “adrenal fatigue” may be a misnomer, though, for what is actually occurring in the body. Fatigue or exhaustion, cortisol imbalance (from testing) along with a history of acute or chronic stress led integrative and functional medicine practitioners to the idea that the adrenal glands were “fatigued” and eventually “exhausted” from constantly producing and dumping the stress hormone cortisol during periods of mental or emotional strain or tension. The thought was that prolonged adverse or very demanding circumstances, over the course of weeks, months, or years, would cause the adrenal glands to become dysregulated and lose normal function due to being “tapped out” and depleted. Through much research and treating increasing numbers of these patients in clinical practice, medical professionals now know the problem involves more than just the adrenal glands. The term hypothalamic-pituitary-adrenal or HPA axis dysfunction more clearly defines what is going on as its scientific backing indicates problems in the brain and central nervous system that are major pieces of the wired but tired, often debilitating condition.

What is HPA Axis Dysfunction?

Before we get into the dysfunction portion of this topic, it’s important to understand what the HPA axis is and what parts of the body it refers to.

Hypothalamus – This part of the brain, located at the base near the pituitary gland, plays an imperative role in many bodily functions. Its main job is to regulate hormone production, which affects a number of physiological processes such as body temperature, emotions, appetite, and sleep (among others). The hypothalamus connects the endocrine system to the nervous system.

Pituitary Gland – Sometimes called the “master gland”, the pituitary gland is the central piece of the endocrine system. It takes information from the hypothalamus, makes hormones the body needs, and disperses this information to other glands in the body so they can perform their essential functions.

Adrenal Glands – The adrenal glands are located just above the kidneys. Based on information received from the pituitary gland, the adrenals are in charge of making necessary hormones. While the adrenal glands produce many hormones, the most closely associated hormones with these small glands are adrenaline and cortisol.

These three areas of the body operate together to perform many essential functions across multiple systems, including the regulation of energy and stress levels, metabolism, and immune response. None of them are independent, and each relies on the other (at least in some way, if not directly) to function properly. At the same time, any imbalances across these systems can trigger a domino effect where the other systems are affected. There are three hormone classifications that can signal an imbalance:

Corticotropin-Releasing Hormone (CRH) – CRH is a stress hormone that is also sometimes called Corticotropin-Releasing Factor (CRF). It’s released by the hypothalamus.

Adrenocorticotropic Hormone (ACTH) – ACTH is released by the pituitary gland. The production of this hormone is triggered by the detection of CRH.

Glucocorticoids – Glucocorticoids are steroids released by the adrenal glands, and are triggered by the detection of ACTH. There are many types of glucocorticoids, and cortisol is one of them.

An abundance of one particular hormone can potentially cause issues. For example, if your body produces too much cortisol, your body will be “stuck” in fight or flight mode. This can lead to trouble sleeping or insufficient sleep, weight gain, and mood changes.

One study found that HPA axis dysfunction “has been found in a high proportion” of Chronic Fatigue Syndrome patients. The researchers of that study described the two conditions as being “associated.” The same study found there to be an “increased frequency of HPA axis dysregulation in females,” inferring that gender could play a role in this condition. While there is still much to be learned about HPA axis dysfunction, the researchers specifically noted that “the need for novel treatment strategies such as those which target the HPA axis is clear.”

“The HPA Axis controls everything from our cortisol and adrenaline and sex hormone secretion (from the adrenal glands) to how our body synthesizes those hormonal shifts (the pituitary) to how it responds to those shifts by releasing different hormones that communicate with our thyroid, our ovaries, our digestive tract, our temperature regulation, and even our growth patterns.”

So what does it look like when things aren’t functioning properly in that axis?

HPA Axis Dysfunction Symptoms

There are many different symptoms associated with HPA axis dysfunction, but the most common include:

Fatigue or exhaustion

Unexplained weight gain or loss

Poor sleep quality (even if you’re sleeping, you don’t wake feeling rested)

Trouble sleeping (falling asleep or staying asleep)

Poor immune response

Difficulty handling and/or managing stress

Brain fog (not being able to think clearly or remember things)

Difficulty concentrating

Increased anxiety


Sugar or salt cravings


Poor circulation

Weak nails (that break easily)

Hair loss (sometimes resulting in bald patches)

Those that are familiar with the term “adrenal fatigue” may be thinking that these symptoms sound a lot like those associated with that condition. The research community has never been able to find conclusive evidence that the adrenal glands can actually be fatigued. Because of the lack of affirmative research, many medical professionals wouldn’t use such a diagnosis. What differentiates HPA axis dysfunction from adrenal fatigue as a diagnosis is the research and correlations to other essential functions. The hypothalamus, pituitary gland, and adrenal glands all work together on a daily basis, and it’s known that dysfunction in any of those body parts can cause issues.

It can be complex but may best be described like this: (and I paraphrase the words of Dr. Ashley Margeson, NMD here) “You’re wired, but exhausted at the same time. You crash in the afternoon. You aren’t really that hungry, but then you can’t stop snacking at night. You feel as if you have to make more lists than normal, your sex drive plummets, you forget simple things, and bright lights really start to bother you. Even though you’re feeling exhausted and overtired, you stay up late because you get a second wind and then you wake up once you fall asleep.”

It’s truly a vicious cycle and one that is very difficult to get out of.

What Causes HPA Axis Dysfunction?

The major and most common cause of HPA axis dysfunction is prolonged periods of stress. One of the biggest physical and mental stressors that I see in my patients are those in which mold and mycotoxins have interfered with life and health. Not only are there the physical inflammatory effects from mold exposure but the challenges of clearing the environment and finding a safe place to live can put enormous strain on the HPA axis. Additionally, people in consistently high-stress situations — medical students, attorneys, CEOs, and other C-level executives, and any other high-pressure job are all at risk of experiencing HPA axis dysfunction systems.

HPA Axis Dysfunction Tests

There is no single test for HPA axis dysfunction, but rather it is suspected when the overall hormonal system is imbalanced.  This includes adrenals, thyroid, sex hormone, and growth hormone from the pituitary gland.

HPA Axis Normalization

HPA axis dysfunction is reversible with environmental and lifestyle changes. We do have to revisit our words of clean air, clean food, and clean water.  You cannot get better if these things are not addressed!

Lifestyle Changes

The most important lifestyle change you’ll need to make is to reduce your stress level. Depending on what is causing you stress, this may look different for different people.

Practice Yoga or Meditation

A good place to start is by beginning a meditation or yoga practice (or both). Learning breathing techniques that help keep your stress response under control is a crucial skill to learn in the management of HPA axis dysfunction.

Reduce Primary Stressors

If you have addressed your physical environment, then dig deeper.  If the main source of your stress is something you can cut out of your life (or reduce significantly), then you should consider doing so. This could mean a job change, speaking less often to a high-maintenance friend or family member, or simply making the choice to find time for yourself instead of overextending your commitments. Otherwise, find a way to channel your stress into something positive that helps you relax.

Make Sleep a Priority

Getting restorative sleep each night can be difficult for some, but if you’re experiencing HPA axis dysfunction symptoms, it’s critical to make sleep a priority in your life. Getting the physical rest you need will help your body and systems recover.

Maintain a Balanced Diet

It’s very important for people experiencing HPA axis symptoms to maintain a healthy balanced diet. Now is not the time for extreme dieting. Stick to a natural whole food, Mediterranean style diet, eat plenty of fruits and vegetables, and stay away from processed foods, sugar, and white flour as much as possible. And of course, drink plenty of water to maintain good hydration.

One thing you may want to avoid (or limit) for at least a little while is alcohol. As alcohol is a depressant, it might be a good idea to limit your intake for a bit.


Exercise can be a big stress reliever. Get up and get your body moving for at least 30 minutes each day. It doesn’t have to be rigorous or difficult, but you should do something you enjoy — something that helps you relax and clear your mind. It may be walking, hiking, biking (even if it’s on a stationary bike), or some light, weight training. The point is to move your muscles, increase your circulation, breathe deeply and relax your mind. Exercising daily also helps you sleep better.

Supplements Which Support HPA Axis Function

The most universally accepted supplements for supporting the HPA axis are vitamin C, B-vitamins, and adaptogenic herbs. Adaptogens help to counteract the effect that stress has on our bodies by working to stabilize the hypothalamus, pituitary gland, and adrenal glands. Specifically, adaptogens help to support the body for better resilience, repair, and homeostasis (equilibrium). A great supplement for this is Adrenal Boost formula by Micro Balance Health. Supporting the HPA can help:

  • Protect your brain and memory;
  • Increase energy levels and endurance;
  • Stabilize your mood;
  • Improve cognitive function;
  • Stimulate your central nervous system.

As more than adrenal glands are involved in this process, however, it is important to look at and support each hormonal system, including the thyroid and sex hormones, as well as pituitary function.  Great homeopathic support for all of these is CellTropin.  It may not specifically be for each and all, the overall support it gives makes individual system treatment easier and more effective.

HPA axis dysfunction is a more accepted diagnosis than adrenal fatigue ever was, but because most primary care physicians may treat each symptom individually, they may not be looking for the underlying cause. However, integrative and functional medicine practitioners have known about and have been addressing this condition for at least a decade. They know what it looks like, so they’re better equipped to diagnose it. Integrative experts aim to get to the root of the problem and help correct it, rather than just mask the symptoms.

Comments? Questions? We love hearing from you! Please write to us below or email us at