An Autoimmune Condition and Adrenal Fatigue Syndrome – Part 2

By: Dr. 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 conditionWhile there is no clear cause of an autoimmune condition, there are many factors that come into play when examining the etiology of the disease. As mentioned earlier, factors include a genetic predisposition, and an array of environmental factors from stress, to infection, to issues with the immune system. Often overlooked and seldom considered is the role our adrenal glands in this.

The adrenal glands are located just above the kidneys and control the production and release of the hormone cortisol. When under physical or emotional stress, the hypothalamus acts on the anterior lobe of the pituitary, which secretes and triggers many hormone pathways including ACTH to signal the adrenals to produce cortisol. When sufficient amounts of cortisol are produced, cortisol is able to act on the hypothalamus and turn the signal pathway off. If, however, cortisol production is not sufficient, the pathway is not able to turn off and the upstream hormone ratios are out of balance. This puts pressure not only on the adrenal glands, but also on the upstream glands such as the anterior pituitary, which controls many other hormone regulations that include our thyroid hormone response, bone growth, and sexual development. When these hormones are out of balance, and the ratios with cortisol are affected, it has been associated with incidence of an autoimmune condition including Systemic Lupus Erythematosus, and Hashimoto’s Thyroiditis.

Cortisol, produced by the adrenal glands, is extremely important in supporting the body in times of stress, and especially important is cortisol’s role in immune system suppression. Cortisol down-regulates the immune response. Autoimmune disease is the result of the immune system over-reacting to a stimulus and beginning to attack healthy tissue over time. Usually, the body has checks and balances in place, so that when the immune system is on overdrive, cortisol is able to down-regulate it and bring the response back to balance. This is how the body normally works.
Excessive stress on the body puts a strain on the adrenal glands and alters the balance of hormones along the way.

Adrenal fatigue and the surrounding circumstances are a perfect storm for triggering an autoimmune condition. In advanced adrenal fatigue, cortisol levels are diminished. When the levels are diminished, it is not available to effectively down regulate an overactive immune system, so the immune response can progress unchecked from stage 1 to stage 3. The body becomes inflamed. It should come as no surprise that people who have weak adrenal function are predisposed to an autoimmune condition.

As well, if our body is genetically predisposed to an autoimmune reactivity due to constitutional factors, and there is an environmental trigger that affects the autoimmunity in our body, cortisol is usually able to keep the response low and managed. If, however, we are also suffering from adrenal fatigue concurrently, the cortisol levels are not able to regulate the immune system and it is much easier to lose self tolerance. In this scenario, it is the perfect opportunity for an autoimmune disease to arise, show symptoms, and progress to a worse condition. While adrenal fatigue is not able to directly cause an autoimmune disease, it is important to understand the relationship between cortisol and immune system management.

Adrenal Fatigue as a Result of an Underlying Autoimmune Disease

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

The HPA pathway is triggered when our body encounters a stressful stimulus. Usually, this stimulus is short lived. The hypothalamus, signals the pituitary to release hormones which affect the adrenal glands to produce the hormone, cortisol. Cortisol then travels throughout the body to respond to the stimulus. This includes activating sugar reserves to give our body energy, releasing neurotransmitters such as norepinephrine to keep our brain on alert. Epinephrine is also released as last resort to ready our body for the “fight or flight” response. Cortisol and other glucocorticoids also manage the inflammatory response. They are able to up-regulate anti-inflammatory signals and down-regulate pro-inflammatory chemicals. The result is suppression of the immune system.

In an autoimmune condition, the immune system tends to be working on overdrive. This is especially true if one is in a hyperactive immune state. Because the body is a network of chemical signals, the increase in the immune system causes a high demand for cortisol and glucocorticoids. This activates the HPA axis, and the demands on the adrenal glands become huge. If this demand is chronic, the adrenal glands are not able to keep up with the cortisol output needed to regulate the immune system. A heightened immune state may be due to primary autoimmune condition or foreign objects being placed into the body, such as breast implants, over a long time. The body’s reaction to such foreign object can be negative. It can trigger an autoimmune response with all the classic symptoms of autoimmune disease such as fatigue, joint pain, anxiety, and brain fog, just to name a few. Removal of such objects may give temporary relief and reduction of symptoms. This welcomed relief, however, is often short lived. It is often followed by worsening fatigue and adrenal crashes. Without proper fortification of the adrenal glands ahead of time, the immune heightened state which the body has been accustomed to continues unabated. When combined with preexisting adrenal weakness with low cortisol output, the heightened immune response can trigger increases in reactive metabolites which in turn can lead to adrenal crashes.

Eventually, adrenal fatigue sets in because cortisol production from the adrenal is insufficient to meet the demand needed to calm the heightened immune system response.

Whether it’s autoimmunity that causes AFS, or AFS that weakens the immune response, it is important to see that both can affect each other and create a vicious cycle if not corrected. Unfortunately, conventional medicine often misses the adrenal connection.

Hyperactive Immune State

an autoimmune condition and your immune systemRegardless of whether autoimmune is the cause or result of AFS, it is clear that a healthy immune system is a necessary positive part our body’s defence.

Unfortunately, in a small number of people, the immune system can be on a hyperactive state, well beyond overdrive that it is designed to handle when faced with pathogens or insults. This can lead to serious consequences.

Sufferers in this category are uniquely faced with clinical situation where symptoms of autoimmune condition exist but laboratory test are not supportive. These sufferers are nevertheless diagnosed and treated as if they have autoimmune disease but without focusing on the root cause, positive clinical outcome is elusive. In the presence of AFS, the clinical picture can be very confusing.

Let us take a step back. As mentioned earlier, our immune system is able to detect pathogens that may become active when body is under stress. To protect us , an inflammatory response was initiated to help neutralize any pathogens that may take this opportunity to surface. The immune system’s job is to attack and neutralize a myriad of active and potential pathogens simultaneously. Co-infectious state (such as H pylori and Lyme Disease) and chronic pathogens (such as candida, EBV) flare up will be automatically squashed if our immune system works properly. Most people think of a weak immune system as the cause of recurrent infections or hard to cure infections. This is certainly true. On the flip side, few are aware that a hyperactive immune state can also be problematic. It is in fact a key factor in formation of the perfect storm that leads to inflammation circuit dysregulation.

The body’s immune system tend to be very well designed and cells are trained to recognize and target the enemy while avoiding “friendly fires” and an autoimmune condition. In some people, however, a supercharged immune system may result inadvertently. A hyperactive immune system , well beyond an overload state, can generate an immune response that is more than what the body needs. It can be too much. Certain antibodies, of examples, can experience cross reaction between outside and internal real and perceived pathogens, creating a rampage of “friendly fires”, where normal cells are attacked along with pathogens. This can cause a flare up of symptoms consistent with autoimmune type conditions. In other words, a hyperactive immune system can trigger symptoms resembling an autoimmune condition.

It is important to remember that such events are uncommon. However, when the body’s immune system is in a hyperactive state, and the collateral damage can be significant. Sufferers can begin to experience symptoms a typical autoimmune condition, such as joint pain and fatigue. With a body inflamed from existing microbiome imbalance, GI tract irritation, or reactive metabolite overload, it is hard to fully decipher for sure if there is a true autoimmune disease (such as primary Hashimoto’s’ thyroiditis or Lupus), or just symptoms resembling an autoimmune condition surfacing when the body’s 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 condition symptomsLaboratory tests such as RA, CRP, ANA titers and anti-TPO antibodies may add to the confusion. They may be normal or borderline high in these situations rather than very high in true primary autoimmune state. Other laboratory studies are generally unremarkable. Unfortunately, few clinicians on the alert for this differentiation that depends on a detailed history for proper assessment. 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 by physicians is to jump to the clinical diagnosis of autoimmune disease. There no comprehensive look the body holistically to look out for a hyperactive immune state or AFS.

Patients are often put on steroids and autoimmune medications. Short-term benefit is common, as the hyperactive immune state calms down from anti-inflammatory properties of corticosteroids. Long term use of steroid can be problematic as it can reduce our overall immune response and mask the underlying problem of excessive metabolites in a setting of hyperactive immune state being the true cause. There is a slow but gradual deterioration of the body, especially the inflammation circuit of the neuroendometabolic (NEM) stress response. Over time as it becomes dysfunctional. One organ that is most easily affected is the thyroid.

Autoimmune Thyroiditis

The thyroid gland is one of the organs most vulnerable to be attacked by a hyperactive immune state, leading to low thyroid function. Unfortunately, symptoms of hypothyroid are also prevalent in advanced AFS. In additional, primary thyroid dysfunction also need to be considered as part of the differential diagnosis. Deciphering which is the correct diagnosis is important because recovery approaches are very different for each.

The thyroid glands controls the overall metabolic rate and is responsible for our body temperature regulation. Slight changes in thyroid function can result in fatigue, weight gain and feeling cold on the hypothyroid side and anxiety and heart palpitation on the other extreme. One of the most frequent complaints that bring patients to their doctors is fatigue and lack of energy. Standard medical workup usually a complete metabolic panel to evaluate thyroid function. In a hyperactive immune state, anti-thyroid autoantibodies (also called anti-thyroid antibodies) that target one or more components of the thyroid may be activated. The most significant one being anti-TPO antibodies. It is present in roughly 90% of Hashimoto’s thyroiditis, 10-20% of nodular goiter or thyroid carcinoma, and 75% of Graves’ disease. Clinicians often make the diagnosis of Hashimoto’s thyroiditis based on laboratory test showing anti-TPO antibodies in a clinical setting of fatigue and low energy.

Also should be noted is 10-15% of normal individuals can have high level anti-TPO antibody titer. They do not have primary autoimmune disease like those mentioned above. The high titer can be secondary to a hyperactive immune system when our inflammation circuit is on overdrive. These patients can be mistakenly diagnosed as having clinical or subclinical primary Hashimoto’s thyroiditis. an autoimmune condition and the thyroidThyroid replacement are often started. Little consideration is given to alternative causes such as inflammation circuit overload. When symptoms of fatigue improved with thyroid replacement, physicians are mislead into thinking they were on the right track, especially if thyroid laboratory studies starts to normalize. More often than not, high anti-TPO antibody count may not normalize totally, but fatigue improved. Doctors are at a lost, but since patient is feeling better, no further investigation is needed. In other words, normalizing TSH, free T4 and free T3 gives the physician a false sense of compliancy. A persistent high rT3 or anti-TPO titer is disregarded as important in such circumstances. Little attention is placed on investigating whether or not symptoms are caused by a hyperactive immune state trigger by inflammation circuit dysfunction that is clinically accompanied by fatigue that comes from adrenal burnout. Because thyroid replacement tend to help increase energy and normalize laboratory test, there is little interest or need to further consider other differentials until this approach stops working. The entire focus of therapy is on primary thyroiditis alone as presumptive diagnosis.

Without resolving the underlying root cause of possible hyperactive immune state and concurrent adrenal fatigue as secondary causes of symptoms resembling autoimmune disorders, many sufferers will continue to need an ever larger dose of thyroid replacement to keep laboratory numbers normalized and sustained energy over time. This can play out over decades. Many who started on T4 replacement eventually have to advance to combination T4/T3 formulas and ultimately to the most potent T3 replacement to maintain the same energy flow. They feel terrible inside, often wired and tired, only to be told all is well. In other words, thyroid slowdown symptoms are treated as an auto-immune issue based on lab test and symptoms when in reality, it represent a body in trouble with the inflammation circuit. Thyroid replacement merely covered up the symptoms. A holistic approach should be deployed to fully comprehend the root cause and effect a comprehensive long term recovery plan.

Steroid – Friend or Foe

In addition to or in place of thyroid replacement therapy, one of the first lines treatment for autoimmune disease management is administration of oral glucocorticoids. While this is a valuable short term solution, there are many issues with taking steroids for long term as immunosuppression. The first is a decreased immune system which makes the body more susceptible to common diseases such as a yeast infection, cold, or flu. Other issues include triggering the onset of Cushing’s Syndrome, which can be the result of chronic glucocorticoid use. Cushing syndrome includes a rounded, reddened face, fat accumulation, and decrease in bone density. an autoimmune condition and steroidsTo avoid Cushing Syndrome it is important to use glucocorticoids under the supervision of a health care provider, and not depend on steroid treatment as a long term solution. Therefore, it is important in managing an autoimmune disease to prevent avoid chronic steroid use, while managing effective cortisol levels. It is easy to over-burden the adrenal glands with an autoimmune condition. In proper autoimmune management, the adrenal glands should be supported and functioning effectively to promote sufficient cortisol levels and manage the immune response while taking away the triggers for excessive hyperactive immune state while supporting good immune cells.

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


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