The following has been researched and written by Bob Myers, moderator of the cutting edge T3CM Yahoo group

Root of the Problem

In the realm of alternative health, addressing the root of the issue rather than the symptom is the main objective. However, the deepest and most significant root often ignored is inflammation and immune deregulation.

In conditions such as Adrenal Fatigue aka “adrenal dysfunction or sluggishness”, it is thought that low cortisol is the primary driver of symptoms and is the root cause of the condition. While it is possible for someone to have a clinical hypoadrenal state such as Addisons Disease, for most, low cortisol is the symptom of a dysfunctional immune system and highly inflamed state.

The previous train of thought and most popular concept of adrenal fatigue was proposed by Dr. James Wilson, i.e. the adrenals will tire after prolonged periods stress. While stress and over activation of the HPA Axis (Hypothalamic-Pituatary-Adrenal Axis) certainly does play a role, it may be a bit more complicated than that.

So how does one reach an adrenal fatigue state?

Basically what happens is an over activation of  your sympathetic nervous system (SNS) for a prolonged period of time. The SNS is that which activates your fight-or-flight response in the face of stress, whether the stress is emotional (that which you perceive or anticipate) or biological (illness or injury, for example). This signals activation of the HPA-axis, which in turn leads to higher levels of cortisol and more importantly adrenaline (also known as epinephrine). Adrenaline works in the short term, stimulating your heart muscle and opening up blood vessels and air passages, which in turn increases blood flow to your muscles and oxygen to your lungs. Cortisol is the stronger, longer-acting response which increases cellular blood sugar and helps maintain homeostasis.

Over time, the body communicates with the immune system to also up regulate. And this leads to a pro-inflammatory state.

The reasons for this over activation of the SNS in thyroid patients varies, but primary reasons which I have seen are: emotional stress, menopause, and hypothyroidism. When you combine the three of those factors along with a predisposition to auto-immune issues, you have a very lethal combination. You will see that a large body of patients who suffer from adrenal fatigue are menopausal or post-menopausal women. This is most likely due to the fact that when women go into menopause, their sex hormones (first progesterone, then estrogen) along with other hormones begin to decline relatively fast. This in turn signals adrenaline secretion. In the case of men, declining testosterone would be similar, although it usually does not decline at the same rate.

Additionally, when thyroid function becomes compromised your body will secrete adrenaline in order to compensate and keep your body temperature elevated (which hypothyroidism lowers) as well as keeping other systems functioning in the body (which hypothyroidism slows down). You can see that a combination of any two above (emotional stress, menopause or hypothyroidism) could be very powerful in triggering your sympathetic nervous system. All of this adrenaline secretion leads to a pro-inflammatory state. Inflammation is a normal response by your immune system in response to something harmful, whether viruses, bacteria, or damaged or irritated tissue.

Your immune system, in an attempt to preserve your body, will communicate through inflammatory signals to your hypothalamus and is very up-regulated. Other structures in the brain to start to down regulate thyroid, adrenals, excitatory neurotransmitters, etc. Think about a time in which you got the flu–your immune system during that time was very active and an overly active immune system is very taxing on your energy levels.

How does inflammation inhibit cortisol?

One way is via small molecules called cytokines. Cytokines are immune system “signaling molecules”, strongly involved in cellular communication and regulation. Some are composed of protein, others are mostly peptides. There are hundreds of these powerful signaling molecules and our very survival depends on them. They can both promote cortisol secretion, as well as inhibit cortisol signaling at your brain and adrenal level.

In the brain, the cytokines can inhibit a structure located in the hypothalamus called the Paraventricular Nucleus, or generally referred to as the PVN, I’ll touch back on this later.

Like everything else we need to balance those cytokines. A dysfunctional immune system will signal for higher levels of certain cytokines while suppressing others. Certain cytokines such at TGF-B1 (Transforming Growth Factor Beta One) can inhibit not only cortisol secretion but also aldostersone secretion. Then you have cytokines such as TNF-a (Tumor Necrosis Factor Alpha) which can attach itself to ACTH receptors on the adrenal gland and prevent cortisol secretion. Elevated levels of TNF-a are strongly associated with low morning levels of cortisol.

Certain cytokines such as Interluekin-10 (IL-10) can keep other proinflammatory cytokines at bay while also signaling cortisol secretion. This cytokine in specific can become smothered in people who have adrenal fatigue by other cytokines from the TH1 side of the immune system, which are acting aggressively. One of the functions of IL-10 is to keep the pro-inflammatory cytokines from the TH1 from over reacting. When pro-inflammatory cytokines are not put in check they can run rampant.

Some researchers are even beginning to theorize that over time our HPA-axis will numb itself to certain cortisol signaling cytokines such as (IL-3) and (IL-6) in order to preserve our body from prolonged exposure to cortisol. Cytokines are also strongly linked to other symptoms that are generally attributed to low cortisol, things like iron dumping, sleep disturbances, low appetite, hair loss and muscle wasting.

More to come….