Autoimmune Disease and Adrenal Fatigue Syndrome – Part 2

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM


Read Part 1 | Part 3

Autoimmune Condition Progression as a Cause of Adrenal Fatigue

The progression of an autoimmune diseaseAlthough there is no clear cause of an autoimmune disease, upon examining the etiology of the disease, many factors clearly come into play. As mentioned earlier, factors include genetic predisposition and an array of environmental factors ranging from stress and infections to immune system issues. Often overlooked, and seldom considered, is the role of our adrenal glands.

The adrenal glands are located just above the kidneys and control the production and release of the hormone cortisol. During physical or emotional stress, the hypothalamus acts on the anterior lobe of the pituitary gland causing it to secrete certain hormones and trigger numerous hormone pathways, including the adrenocorticotropic hormone (ACTH) pathway, which signals to the adrenals to produce cortisol. After a sufficient amount of cortisol is produced, cortisol act on the hypothalamus to turn off the pathway. However, if the amount of cortisol produced is not sufficient, the pathway is not turned off and the upstream hormone ratios become out of balance. This puts pressure on the adrenal glands and upstream glands such as the anterior pituitary gland, which regulates many other hormone pathways including the thyroid hormone response, as well as the hormone responses controlling bone growth and sexual development. Hormonal imbalances and unusual cortisol to other hormone ratios have been associated with the incidence of autoimmune conditions including SLS and Hashimoto’s thyroiditis.

Cortisol, produced by the adrenal glands, is extremely important in supporting the body during times of stress, and cortisol plays a particularly important role in suppressing the immune system by downregulating the immune response. Autoimmune disease is the result of the immune system overreacting to a stimulus and attacking healthy tissue over time. Usually, the body puts checks and balances in place to ensure that when the immune system is on overdrive, cortisol is able to downregulate the immune system and bring back the balance. This is how the body normally works. However, excessive stress on your body puts strain on the adrenal glands, thus, altering the balance of hormones along the way.

Adrenal Fatigue and surrounding circumstances can be a perfect storm for triggering an autoimmune disease. In advanced Adrenal Fatigue, cortisol levels are diminished and not available to effectively downregulate an overactive immune system. Therefore, the immune response can progress unchecked from stage one to stage three, inflammation can occur, and it should come as no surprise that people who are predisposed to an autoimmune disease also have weak adrenal function.

Moreover, if your body is genetically predisposed to autoimmune reactivity due to constitutional factors and there is an environmental trigger affecting the autoimmunity of your body, cortisol can usually keep the response low and manageable. However, if you are also suffering from Adrenal Fatigue, your low cortisol levels will not be able to regulate the immune system and it’s much easier to lose self-tolerance. This scenario presents the perfect opportunity for an autoimmune disease to arise, trigger symptoms, and progress into a much worse condition. Whereas Adrenal Fatigue does not directly cause an autoimmune disease, however, it’s important to understand the relationship between cortisol and immune system management.

Adrenal Fatigue as a Result of an Underlying Autoimmune Disease

An autoimmune disease leading to adrenal fatigueAs mentioned above, AFS can be the result of chronic stress on the body due to either an external stressor, such as a stressful work environment, relationship stress, or family stress, or an underlying cause of stress on the body, such as a chronic infection or chronic disease like an autoimmune disease.

The HPA pathway is triggered when our body encounters a stressful stimulus. Usually, the stimulus is short lived. The hypothalamus signals to the pituitary to release hormones that affect the adrenal glands, which subsequently produce the hormone, cortisol. Finally, cortisol travels through the body in order to respond to the stimulus. This response may include activating sugar reserves to give your body energy or releasing neurotransmitters such as norepinephrine to keep your brain on high alert. Epinephrine is also released as a last resort to prepare your body for the “fight or flight” response. Cortisol and other glucocorticoids also manage the inflammatory response by upregulating anti-inflammatory signals and downregulating pro-inflammatory chemicals. The result is suppression of the immune system.

With autoimmune conditions, the immune system tends to work on overdrive, especially if your body is in a hyperactive immune state. Because the body has a network of chemical signals, an increase in immune response causes high cortisol and glucocorticoid demand. This activates the HPA axis and results in huge demands on the adrenal glands. If the situation becomes chronic, your adrenal glands will no longer be able to keep up with the high cortisol output needed to regulate the immune system. A heightened immune state may be due to a primary autoimmune condition but can also be the result of foreign objects being placed into the body, such as breast implants that remain for a long period of time. Your body may react negatively to these foreign objects and trigger an autoimmune response, characterized by all the classic symptoms of an autoimmune disease, such as fatigue, joint pain, anxiety, and brain fog, just to name a few. Removing foreign objects may give temporary relief and reduce symptoms. However, although welcome, the relief is often short lived and followed by a worsening of fatigue and adrenal crashes. Without properly fortifying the adrenal glands ahead of time, the immune heightened state the body has become accustomed to continues unabated. When pre-existing adrenal weakness is combined with low cortisol output, the heightened immune response can trigger an increase in reactive metabolites, which, in turn, may lead to adrenal crashes.

Eventually, Adrenal Fatigue sets in because the amount of cortisol produced by the adrenals is insufficient to meet the demands of a heightened immune system response.

Whether autoimmunity has caused AFS, or AFS has weakened your immune response, it is important to recognize that both of these conditions can affect each other, often creating a vicious cycle if left uncorrected. Unfortunately, conventional medicine often misses the adrenal connection.

Hyperactive Immune State

An autoimmune disease and your immune systemRegardless of whether autoimmunity is the cause or result of AFS, a healthy immune system is a crucial part your body’s defense.

Unfortunately, in a small cohort of people, the immune system is in a hyperactive state far beyond what it was designed to handle when faced with pathogens or insults. This can lead to serious consequences.

Sufferers in this category are uniquely faced with a clinical situation in which the symptoms of an autoimmune condition exist but laboratory tests do not support the symptoms. Nonetheless, these sufferers are diagnosed and treated as if they have autoimmune disease without focusing on the root cause, therefore, positive clinical outcomes are elusive. In the presence of AFS, the clinical picture can be very confusing.

Let’s take a step back. As mentioned earlier, our immune system is able to detect pathogens that may become active when the body is under stress. To protect us, an inflammatory response is initiated to neutralize any pathogens that have taken the opportunity to surface. The job of the immune system is to simultaneously attack and neutralize a myriad of active and potential pathogens. If your immune system is working properly, flare-ups of co-infectious states (such as Helicobacter pylori and Lyme disease) and chronic pathogens (such as Candida or EBV) are automatically squashed. Most people are aware that a weak immune system is the cause of recurrent infections or hard to cure infections. And this is certainly true. However, on the flip side, few people are aware that a hyperactive immune state can also be problematic. It is, in fact, a key factor in forming the perfect storm that leads to inflammation circuit dysregulation.

The body’s immune system tends to be very well designed and your immune cells are trained to recognize and target enemies while avoiding “friendly fire” and an autoimmune condition. In some people, however, a supercharged immune system may result in adverse effects. A hyperactive immune system, far beyond the state of overload, can generate an immune response that is more intense than what the body actually needs—too much. Certain antibodies, for example, experience cross reactivity between actual and perceived pathogens, external and internal, creating a rampage of “friendly fire,” whereby normal cells are attacked along with the pathogens. This can lead to a flare up of symptoms consistent with the symptoms of autoimmune-type conditions. In other words, a hyperactive immune system can trigger symptoms resembling an autoimmune condition.

It’s important to remember that this type of event is uncommon, however, the collateral damage caused by a hyperactive immune state can be significant. Sufferers may start to experience symptoms typical of an autoimmune condition such as joint pain and fatigue. Moreover, if your body is already inflamed due to an existing microbiome imbalance, GI tract irritation, or reactive metabolite overload, it’s difficult to know for sure whether a true autoimmune disease (such as primary Hashimoto’s’ thyroiditis or Lupus) exists or just symptoms resembling an autoimmune condition, which surface every time good cells are attacked in the crossfire.

When your immune system is in a hyperactive state, you can start to experience fatigue, one of the typical autoimmune disease symptomsLaboratory tests, such as RA, CRP, ANA titers and anti-TPO antibodies, often add to this confusion. In this type of situation, antibodies may be normal or borderline high rather than very high in a true primary autoimmune state. Other laboratory studies are generally unremarkable. Unfortunately, accurate diagnosis depends on a detailed history to properly differentiate and few clinicians are on the alert for minor differences that can differentiate a true autoimmune disorder from Adrenal Fatigue. When normal or borderline high laboratory tests are accompanied by fatigue, joint pain, psoriasis, gastric discomfort, weight gain, vasculitis, and muscle ache, the knee-jerk reaction of most physicians is to clinically diagnose an autoimmune disease. The body is not always viewed in the comprehensive or holistic way required to diagnose a hyperactive immune state or AFS.

Patients are often put on steroids and autoimmune medications and short-term benefits are common as the hyperactive immune state calms down due to the anti-inflammatory properties of corticosteroids. Long-term use of steroids can be problematic since it can reduce your overall immune response and mask the underlying excessive metabolite problem if a hyperactive immune system is the true cause. Slow and gradual deterioration of the body occurs, in particular, over time, the inflammation circuit of the NeuroEndoMetabolic (NEM) stress response becomes dysfunctional. The thyroid is the most easily affected.

Autoimmune Thyroiditis

The thyroid gland is one of the organs most vulnerable to attack by a hyperactive immune state, leading to low thyroid function. Unfortunately, symptoms of an underactive thyroid are also prevalent in advanced AFS. In addition, primary thyroid dysfunction must be considered as part of a differential diagnosis. Since recovery approaches are very different for autoimmune conditions and AFS, identifying the correct diagnosis is important.

The thyroid gland controls your overall metabolic rate and is responsible for regulating body temperature. Therefore, even slight changes in thyroid function can result in fatigue, weight gain, and feeling cold, in the underactive case, or anxiety and heart palpitations, in the overactive case. One of the most frequent complaints that brings a patient to their doctor is fatigue and a lack of energy. The standard medical workup usually includes a complete metabolic panel to evaluate thyroid function. In a hyperactive immune system, anti-thyroid autoantibodies (also called anti-thyroid antibodies) targeting one or more components of the thyroid gland may be activated. The most significant are the anti-TPO antibodies—present in roughly 90% of Hashimoto’s thyroiditis, 10-20% of nodular goiter or thyroid carcinoma, and 75% of Grave’s disease. Clinicians often make a Hashimoto’s thyroiditis diagnosis based on laboratory tests showing upregulation of anti-TPO antibodies accompanied by fatigue and low energy.

It should also be noted that 10-15% of normal individuals have high levels of anti-TPO antibodies but do not have a primary autoimmune disease like those mentioned above. The high titer can be secondary to a hyperactive immune system when the inflammation circuit is working on overdrive. Often, patients are mistakenly diagnosed with clinical or subclinical primary Hashimoto’s thyroiditis and thyroid hormone replacement is started. An autoimmune disease and the thyroidLittle consideration is given to alternative causes such as inflammation circuit overload. When symptoms of fatigue improve with thyroid hormone replacement, physicians are misled into thinking they are on the right track, especially if laboratory test results begin to normalize. More often than not, although fatigue improves, high anti-TPO antibody count does not totally normalize. Doctors are at a loss, however, and since the patient feels better, no further investigations are performed. In other words, normalizing TSH, free T4, and free T3 gives the physician a false sense of compliance. Persistently high rT3 or anti-TPO titers are disregarded in such circumstances and little attention is paid to whether symptoms are caused by a hyperactive immune system-triggered adrenal burnout—inflammation circuit dysfunction accompanied by fatigue. Since thyroid hormone replacement tends to increase energy levels and normalize laboratory test results, until the approach stops working, there is little interest or need to further consider other differentials. The entire therapeutic focus is on primary thyroiditis alone as the presumed diagnosis.

Without resolving the underlying root causes of a possible hyperactive immune system and Adrenal Fatigue as a secondary causes of symptoms resembling an autoimmune disorder, many sufferers continue to require ever-increasing doses of thyroid hormone replacements over time to maintain normalized laboratory test results and sustain energy levels. This can play out over decades and to maintain the energy levels, many start on T4 replacement, eventually advancing to combination T4/T3 formulas, and ultimately, progressing to the most potent T3 replacement. Although sufferers may feel terrible inside and are often wired and tired, they are told all is well. In other words, based on lab tests and symptoms alone, thyroid slowdown symptoms are treated as an autoimmune issue when in reality may indicate issues with the inflammation circuit. Thyroid hormone replacement merely covers up the symptoms. Therefore, a holistic approach should be used to fully understand the root cause of symptoms and to develop a comprehensive long-term recovery plan.

Steroids – Friend or Foe

In addition to or in place of thyroid hormone replacement therapy, one of the first lines of treatment for autoimmune disease is the administration of oral glucocorticoids. Whereas this may present a valuable short-term solution, numerous problems are associated with taking steroids for long term immunosuppression. The first is decreased immune system function making your body more susceptible to common diseases such as yeast infections, colds, and flu. Other adverse effect of chronic glucocorticoid use can be triggering the onset of Cushing’s Syndrome, characterized by a rounded, reddened face, accumulation of fat, and a decrease in bone density. An autoimmune disease and steroidsTo avoid Cushing’s Syndrome, it’s important to only use glucocorticoids under the supervision of a qualified healthcare provider and to not become dependent on steroid treatments as a long-term solution. Therefore, it’s important to avoid chronic steroid use in managing an autoimmune disease, while effectively managing cortisol levels. With an autoimmune condition, it’s easy to overburden the adrenal glands. To properly manage autoimmune conditions, the adrenal glands must be functioning effectively. The adrenals should be supported to ensure sufficient cortisol levels and manage the immune response, and at the same time, any triggers that may lead to a hyperactive immune system should be removed while supporting good immune cells.

Read Part 1 | Part 3

© Copyright 2017 Michael Lam, M.D. All Rights Reserved.


Autoimmune disease