Adrenal Fatigue

Your adrenal glands are like the spark plugs in your car. They give your body energy so that it can run, metabolize, move, exercise, concentrate and so much more. However, if pushed too hard, the nervous system that relates to your adrenal glands can begin to suffer. This leads to symptoms related to low energy, depression, lethargy, brain fog, that “wired-and tired” feeling and so much more. Let’s talk about integrative treatments for adrenal pathway health including supplements for adrenals, herbs for adrenals, and diet and your adrenal gland.

  • If you are ready to get to the root cause of why you feel exhausted, this page is for you. 
  • If you have received a lab test result that shows low cortisol then this page is for you. 
  • If you have seen many integrative clinicians with limited success then this page is for you.
  • If you have been diagnosed with adrenal fatigue, then this page is for you. 

The first thing that I have to tell you might be quite different from what your other doctors have explained. There is no such thing as adrenal fatigue.

I imagine that as some of you are reading these first few sentences that you may be thinking: 

“Of course adrenal fatigue is a real thing. I’m tired, I get dizzy when I stand up, and my doctor told me that my labs showed low cortisol!”

But what if I were to tell you that you are only getting a small glimpse of the picture? What if your diagnosis of adrenal fatigue is actually the wrong diagnosis? 

Let me start with a story….

Mary was suffering from high anxiety and agitation, mixed with fatigue, brain fog, caffeine dependence, and difficulty sleeping. She had done extensive research and was absolutely positive she had adrenal fatigue. In fact, she had been told by a doctor years prior that she had adrenal fatigue and had been prescribed supplements that offered only minimal relief. Mary came to my office with a list of symptoms that she suffered with and showed me how they matched published symptoms of adrenal fatigue: fatigue with trouble waking up, insomnia at night time, weight gain, cravings for sugar and salt, and others. We ran some lab work and the findings were fascinating. She did not have adrenal fatigue- in fact, her adrenals were producing ample amounts of cortisol. But she did have low active cortisol. 

In this article we will be discussing the following:

  • What are the adrenal glands?
  • How do the adrenals work?
  • What does cortisol do?
  • What are the symptoms of high cortisol?
  • What are the causes of high cortisol?
  • What are the symptoms of low cortisol?
  • What are the causes of low cortisol?
  • What is adrenal fatigue?
  • Integrative treatments for adrenal health.

What Are the Adrenal Glands?

The adult adrenal gland weighs approximately 4-5 grams and you have one atop each of your two kidneys. Your adrenal gland is somewhat triangular shaped and is made up of a medulla on the inside and a cortex surrounding the outside. The medulla releases hormones called catecholamines, including adrenaline, norepinephrine, and dopamine. The cortex releases mineralocorticoids like aldosterone, glucocorticoids like cortisol, and androgens including DHEA and testosterone.

The job of the adrenals is vast, as they regulate many systems in your body. As you can imagine, if the adrenals are not working properly, you may experience body-wide symptoms.

Let’s discuss in brief, a little bit about adrenal physiology. 

How Do the Adrenals Work?

There is a pathway in your body called the hypothalamic-pituitary-adrenal (HPA) axis. This axis is responsible for regulating your adrenal function. 

For purposes of this article, we will focus on the stress response: The most important hormone in helping your body respond to stress is the hormone cortisol

When the body is in need of cortisol, the hypothalamus in your brain releases a hormone called corticotropin-releasing hormone (CRH). CRH stimulates the pituitary gland to produce ACTH (adrenocorticotropic releasing hormone), which then goes to the cortex of your adrenal glands and stimulates them to make cortisol

After there is enough cortisol hormone available, cortisol then, via a negative feedback loop, inhibits both CRH and ACTH production. 

This feedback loop allows the HPA axis maintains a delicate balance in not allowing your adrenals to produce too much or too little cortisol. 

The Hypothalamic Pituitary Axis (HPA Axis)

What Does Cortisol Do?

We’ve learned so far, that your adrenals produce cortisol in order to aid in the stress response. Cortisol is able to achieve this by working with many systems in your body. Here is a short (and incomplete) list of all of the things that cortisol does in your body: 

  • Cortisol works with aldosterone to control the salt-water balance in your body which impacts kidney function and blood pressure. 
  • Cortisol also regulates your blood sugar by breaking down stored energy, called glycogen, into useable energy in the form of glucose. 
  • Cortisol regulates your metabolism
  • Cortisol reduces inflammation
  • Cortisol aids in the formation of memories and impacts focus and cognition
  • Cortisol stimulates the dopaminergic (dopamine) system 
  • Cortisol stimulates the amygdala (the emotional center of the brain)
  • Cortisol converts inactive T4 thyroid into active T3 thyroid 
  • Cortisol release stimulates the glucocorticoid-responsive elements (GREs) within the DNA (which can then change methylation and gene expression to cause chronic anxiety), and so much more. 

All of these changes (and many more) are coordinated in a symphony of biochemical and physiological changes that enable you to respond appropriately to internal and external stressors.

There are diseases that can cause cortisol to go too high, as well as too low. 

What are the symptoms of high cortisol?

High cortisol aka hypercortisolism is associated with symptoms that can impact you head to toe. Symptoms of high cortisol may include: 

  • High blood pressure
  • High blood sugar
  • Frequent urination
  • Increased thirst
  • Increased fat around the base of the neck
  • Round face
  • Easy bruising
  • Wide purple stretch marks (especially on the abdomen)
  • Muscle weakness
  • Rapid weight gain (especially abdomen and face)
  • Osteoporosis
  • Mood changes like Agitation/ anger, anxiety
  • Sleeping issues: Insomnia, restless legs 
  • etc.

What Causes High Cortisol?

High cortisol is called hypercortisolism. We are able to measure cortisol in the blood, saliva, and urine. Elevated cortisol can be life-threatening and identifying the exact cause is imperative in designing an effective treatment.

Below are two of the most important causes of high cortisol:

  • Cushing’s Syndrome: The most common cause of excessive cortisol is seen in a condition called Cushing’s Syndrome. Cushing’s Syndrome occurs after the body has been exposed to too much cortisol over a long period of time. Common symptoms of Cushing’s syndrome include High blood pressure, high blood sugar, increased fat around the base of the neck, round face, easy bruising, wide purple stretch marks (especially on the abdomen), muscle weakness, and weight gain. Cushing’s Syndrome can be caused by medications or by a tumor. The tumors may occur on the lung or adrenal glands (or elsewhere in some cases), and they produce the hormone ACTH. Remember that ACTH is involved in the pathway of cortisol production. However, ACTH that comes from a tumor does not respond to the negative feedback loop and therefore cortisol levels continue to rise and serious symptoms result.
  • HPA Axis Disease: As discussed, your body uses the hypothalamic-pituitary-adrenal (HPA) axis in coordination with its stress response. When this system is activated the cortex of the adrenals releases glucocorticoids– the chief of which is cortisol. We have learned that cortisol coordinates a multitude of processes that are necessary for survival. 

Problems arise when interfering variables activate and interfere with this complex system. For example, research has shown that cytokines, which are immune system cells that regulate inflammation, are able to potently activate the stress response. Specific cytokines implicated include TNF-alpha, Interleukin 1 beta, and Interleukin-6. Glucocorticoids are known to be effective immunosuppressants and immunomodulators. Once glucocorticoid levels are triggered and rise, they then in turn reduce inflammation. 

What are the symptoms of low cortisol?

Low cortisol is also called hypocortisolism or glucocorticoid deficiency. When cortisol is too low we can see symptoms including (but not limited to): 

  • Hyperpigmentation of the skin and gums, for example, we often see an orange tint to the skin in individuals suffering from Addison’s disease– the most common condition associated with adrenal hypofunction.  
  • Hypoglycemia (low blood sugar)
  • Hypotension (low blood pressure)
  • Orthostatic hypotension, which is where the blood pressure drops when you rise from sitting to standing
  • Recurrent infections
  • Rapid weight loss 
  • Fatigue

What Causes Low Cortisol (Hypocortisolism)?

There are many reasons cortisol levels can drop, here are some of the most common causes:

  1. Estrogen: Once produced, most of your cortisol travels through circulation bound to proteins, they are called albumin and cortisol-binding globulin (CBG-transcortin). When cortisol is bound to a protein it is inactive, it only becomes active when becoming unbound. One of the main causes of low cortisol is due to estrogen. This occurs because estrogen causes cortisol to bind to proteins. protein-bound cortisol is inactive cortisol and resulting symptoms are those that we typically associate with “adrenal fatigue.” For example, if a woman is taking birth control or hormone replacement therapy and has high estrogen, she may suffer from symptoms that look like she has low cortisol levels.

Estrogen levels rise → stimulates cortisol to bind to proteins = cortisol is inactivated.

  1. Cortisol is converted to cortisone: 11 beta-hydroxysteroid dehydrogenase (HSD-11B) (11B-HSD) is an enzyme family that converts cortisol to cortisone and vice versa. When cortisol is converted into cortisone you may develop symptoms of inadequate cortisol. Glycyrrhiza (licorice) inhibits HSD-11B however you have to be careful and keep an eye out to ensure cortisol levels do not rise too high, over bind to mineralocorticoid receptors, and cause not only symptoms of cortisol excess, but also symptoms of mineralocorticoid overstimulation which includes low blood potassium, high blood pressure, and alkalosis.

Cortisol → converted by HSD-11B → to Cortisone = less cortisol in circulation

  1. Dysfunction of the hypothalamus of the brain: The hypothalamus is a part of your brain and is located near the pineal gland. The hypothalamus is involved in many activities including Regulating hormones, body temperature, coordinating the stress response, controlling appetite, modulating neurotransmitter release, etc. Your hypothalamus is a part of the HPA Axis, and as mentioned above, it releases CRH to the pituitary. Hypothalamic hypofunction is when the hypothalamus is not doing its job properly. This may be caused by many things, for example, malnutrition, anorexia, bulimia, genetic disorders, head trauma (concussions), radiation, tumors, or aneurysms. If the hypothalamus does not release adequate CRH, then downstream we may see reduced cortisol output from the adrenal glands.

Inadequate CRN → Pituitary = Reduced ACTH = Reduced Cortisol from Adrenals

  1. Pituitary gland dysfunction: As we discussed above, the pituitary gland is a part of the HPA Axis. In response to CRH, the pituitary gland releases ACTH which goes to the adrenal glands and stimulates them to make glucocorticoids, principally, cortisol. If the pituitary is not functioning optimally, it may not release adequate ACTH to the adrenals, and therefore you may suffer from symptoms of low cortisol. Causes of pituitary hypofunction may include Brain tumors, aneurysm, meningitis, radiation treatment, chemotherapy, tuberculosis, and genetic condition.

Reduced Pituitary ACTH = Reduced Cortisol from Adrenals

  1. Adrenal insufficiency: True adrenal insufficiency occurs when there is a deficiency in cortisol hormone production by the adrenal glands. This may be caused by primary adrenal disease, pituitary hypofunction, or hypothalamic disease. The most common disease associated with adrenal insufficiency is called Addison’s Disease. In Addison’s Disease, we see symptoms of low cortisol as well as low aldosterone. Symptoms of Addison’s disease include Extreme fatigue, weight loss, hyperpigmentation (or darkening) of your skin, low blood pressure (due to aldosterone insufficiency), salt cravings, low blood sugar, and much more. Addison’s Disease is caused by adrenal gland disease and autoimmune diseases where the body’s immune system attacks your adrenal glands.

Adrenal gland hypofunction: 

Primary Adrenal Disease, for example, Autoimmune attack against adrenals

Dysfunction in the HPA Axis

  1. Impairment in the negative feedback loop of the HPA: There was an interesting study published in the journal of Psychosomatic Medicine, conducted by Burke et al, which described that the cortisol response was blunted in individuals who exhibited extremely high levels of depressive symptoms. This finding was discussed further by Dekel et al in their publication in the journal Psychosomatic Medicine, and they stated: “Blunt cortisol associated with depressive symptoms may relate to mechanisms of psychological disengagement with environmental stressors (Burke et al., 2005) and excessive shutting down of the hypothalamic-pituitary-adrenal cortical (HPA) axis due to impairment in negative feedback.” 

Impairments in the negative feedback loop interfering with the HPA Axis. 

Okay… So What is Adrenal Fatigue?

We’re finally getting to the adrenal fatigue section of this article. Now that you’re an expert on all-things-adrenal, we can finally discuss the mythology of adrenal fatigue. 

The term adrenal fatigue came into popularity in the 1990s when Chiropractor James L. Wilson observed a cluster of symptoms in his patients. He theorized that constant stress (emotional, or physical) puts pressure on the adrenal glands, whose job is in part to respond to stress by producing the stress hormone, cortisol. 

He states that the adrenal glands get burnt out causing a decrease in adrenal hormone production. 

However, there is no evidence that this happens. In fact, as we’ve discussed, the evidence actually points to the contrary: your adrenals make more cortisol under stress. Not less. 

Let’s explore this in a little more detail:

The symptoms that patients report getting diagnosed with adrenal fatigue–poor sleep, weight gain, sluggishness, anxiety, nervousness, and extreme fatigue– are not the same symptoms that are associated with true adrenal insufficiency

Remember, the symptoms of actual adrenal insufficiency included things like low blood sugar, low blood pressure, and weight loss

In fact, most of the symptoms of “adrenal fatigue” actually result from life choices: poor eating habits, poor sleep habits, and no exercise. 

You may be asking: So what does all this mean? Why was my cortisol low on my test?

Remember, there are many causes of low cortisol. This can be due to medications, time of day (as cortisol rises in the morning and goes down in the afternoon and towards evening), hormone changes, inflammation, autoimmune disease, and so on and so on. 

If there are abnormalities in your cortisol levels, before buying that bottle of adrenal supplements, talk with your doctor about root-cause testing that might be appropriate. While adrenal fatigue does not technically exist, we can garner useful information from your symptoms. 

Following the naturopathic tenets of health will get you on the right track, and these are the steps that we followed in helping Mary get her life back. They include:

Naturopathic and Integrative Methods for Adrenal Health

  1. Identify the root cause of your symptoms through appropriate assessment and testing
  2. Give the body what it needs: This may include nutrition, minerals, hydration, sleep, etc.
  3. Remove obstacles to cure: This could be internal stressors like toxic build-up, inflammation, use of drugs, alcohol, and even environmental and other external stressors like an abusive relationship or problematic job.
  4. Tonify weak and damaged systems: Give your body the nutrients to help it do what it does best. This means if your liver enzymes are elevated, nutrients to heal the liver will help “tonify” the liver so that it detoxes properly. If your adrenals are producing insufficient cortisol, adrenal support may be temporarily useful. But always be sure to pay attention to the other steps in this guidebook. 
  5. Correct structural integrity: The central nervous system regulates your peripheral nervous system — which includes your organs, nerves, bones, and more. Making sure the nervous system is optimally functioning will set a foundation for optimal peripheral function. 
  6. Stimulate the body’s natural ability to heal itself: This can be done through meditation, mindfulness, stress reduction techniques. One of my favorite quotes is “disease cannot exist in a bliss-filled state.” Your body is designed to heal itself. What can you do to create an optimal foundation for healing to occur?

Summary and Key Points:

  • The adrenals do not become “fatigued” but there are many causes of levels of cortisol in the body.
  • Addison’s Disease is the most common condition associated with low cortisol. 
  • Inflammation interferes with the HPA axis which can change cortisol release
  • High estrogen (biologically, or from HRT or birth control) is associated with increased binding of cortisol to carrier proteins, thus inactivating the cortisol.
  • Excessive activity of 11 beta-hydroxysteroid dehydrogenases (HSD-11B) results in active cortisol being converted into inactive cortisone.
  • There are incredible botanicals that can promote HPA axis function, block HSD-11B, and improve cortisol production and metabolism.

Check out these adrenal support supplements!*

References

Asprey, D. (n.d.). “You Might Have Adrenal Fatigue, Here’s How to Treat it Naturally.” Retrieved from

https://blog.bulletproof.com/adrenal-fatigue-treatment-symptoms/

Greer, M. (2011). “Herbal Options for Managing Adrenal Fatigue.” Retrieved from

https://holisticprimarycare.net/topics/topics-a-g/chronic-disease/1241-herbal-options-for-managing-adrenal-fatigue.html

Hansen, F. (2017). “How to use Licorice Root for Adrenal Fatigue.” Retrieved from

https://adrenalfatiguesolution.com/licorice-root-adrenal-fatigue/

Panossian, A., & Wikman, G. (2010). Effects of Adaptogens on the Central Nervous System and the

Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals (Basel, Switzerland), 3(1), 188-224. doi:10.3390/ph3010188

*Always talk with your doctor before making any changes to your protocol.