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ADRENAL FATIGUE– HPA Axis Dysregulation

When faced with a complicated medical concept there is the temptation to use a simple explanation to cut through the layers of complexity. As our knowledge on the topic expands these original over-simplified explanations can actually become detrimental in the understanding of the concept at hand. The use of “adrenal fatigue” and “adrenal exhaustion” is one example. Although these terms have been helpful in dispelling the myth that only extreme issues relating to adrenal function such as Addison’s or Cushing’s disease are relevant, they should now be replaced by more medically appropriate terms such as HPA axis dysregulation.

The purpose of your HPA axis is to help your cope with stressors and survive. Note I said stressors as there are often many different sources of stress. However, the important thing to remember is that the stress response is always the same, no matter where the stressor is coming from.


Stress is everyone’s inferno, tormenting our minds, igniting our nights and upending our equilibrium. But it hasn’t always been so, once its purpose was to save us. The stress response in humans and other mammals was really designed to deal withthe 3 minutes of screaming terror on the African savannah when confronted with a lion, after which it’s over with or you’re over with.

Through their pioneering work on the effects of stress on human health, Nobel Prize nominee Hans Selye together with Walter Cannon identified how the stress response is at the root of every chronic disease. Although the sources of stress can vary, the body’s response is always the same.

Walter Cannon (1871 – 1945) coined the term “Fight or Flight” referring to a perceived harmful event or attack and the action of the sympathetic nervous system producing a hormonal cascade of adrenaline, noradrenaline, cortisol and DHEA amongst others.

This stress response and the actions of the sympathetic nervous is designed for short bursts after which the parasympathetic nervous system takes over to return as to homeostasis and allow us to rest and repair from the previous stressful encounter.

In today’s society everything about the normal healthy stress response has changed. Insult after insult to the stress response is causing chronic health disease at an alarming rate.

There are three basic ways that the stress response becomes damaged leading to HPA dysfunction :

  1. Frequent and repeated stressful events reduce your ability to adapt to stress.
  2. A stress response that does not resolve or turn off
  3. An inadequate or failure to respond to a stressor

Stress is not just a concept or a state of mind, it is measurable and as already shown can be dangerous when left unmanaged. Functional lab testing can measure the levels of these stress hormones and determine how much prolonged stress you have been under.

Although there are a myriad of stressors they can be divided into three main categories;

  1. Emotional Stress:

 Unfortunately this is the most common type of stress in today’s society. Mental, emotional and psychosocial stressors are greatly influenced by past history of stress or trauma, by learned behaviours, by personality traits or possibly by neurotransmitter imbalances. This type of stress maybe described as fear, worry, anxiety, anger, pressure, hopelessness or anger. These are perceived threats not actual physical threats which is classically what the stress response was designed for.

 The most common sources of perceived threats are related to employment, relationships, financial problems, traumatic memories, social life or even dealing with Sydney traffic.

 Although not of a physically threatening nature these perceived threats can be life destroying due to the activation of the stress response and loss of health that results

  1. Dietary Stress:

All of us have been guilty of grabbing a take away coffee and a pastry for breakfast when rushing to make a flight or get the train to work.

 This huge surge in blood glucose levels results in insulin being released to counterbalance the effect of this surge in blood sugar. This roller coast ride of surging blood sugar followed by a huge crash will set the stage for HPA axis dysregulation (adrenal fatigue)

 Dietary stress and glycaemic dysregulation are extremely common and you will often not even realize it is happening. Every time you feel under stress and reach for a high-fat, high-sugar or high-salt food you are setting yourself up for HPA axis dysfunction, insulin resistance and obesity. This inter-relationship between the stress response and glycaemic dysregulation is perhaps the most overlooked contributors to HPA axis dysregulation.

 There is a rising epidemic of insulin resistance and obesity. In fact Type II diabetes is now the fastest growing chronic disease on this planet.

  1. Pain & Inflammation

Cortisol is a powerful anti-inflammatory steroid. Most of you aware of the use of cortisone injections to act as an anti-inflammatory. Acute or chronic inflammatory signals will trigger the HPA axis with a purpose to increase cortisol availability within inflamed tissues. This inflammation goes unnoticed by the patient as it’s not something you can see or necessarily feel. Many people suffer from joint pain, neck and pain when imbalances in cortisol exist.

Inflammation can have many sources including;

  • the digestive system due to food allergies or a bacteria or pathogen,
  • chronic low level inflammation due to obesity
  • cardiovascular disease and inflammation
  • joint damage and resulting inflammation from arthritis
  • asthma
  • auto immune disease
  • inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis
  • sinusitis


The most commonly experienced symptoms of adrenal stress include;

  • fatigue
  • depression
  • inability to lose weight
  • craving sweet or salty foods
  • decreased sex drive
  • insomnia
  • poor memory
  • anxiety
  • PMS
  • Weakened immune response
  • Recurrent infections
  • Unexplained nervousness or irritability
  • Joint and muscle pain


This three stage model often used in Functional Medicine is based on the pioneering work of Hans Selye and his General Adaptation Syndrome (GAS) of chronic stress.

Stage 1: Often known as the alarm phase, years of chronic unrelenting stress activation, whether it be emotional, dietary or inflammatory will cause an increase in cortisol. During stage 1, levels of DHEA will be decreasing signalling adaptation to the chronic stress response.

Stage 2: Also termed the Resistance phase can be thought of as stress maladaptation. ACTH a hormone that is secreted by the Pituitary gland to signal to the adrenal glands to release cortisol starts to become diminished and cortisol levels start to plummet. As discussed before, HPA axis dysfunction is a far more accurate term than adrenal fatigue.

In stage 2 cortisol levels may look within the normal range but they are dropping together with DHEA levels.

Stage 3: Typified by exhaustion and complete burnout is where the HPA axis has become down-regulated and levels of both cortisol and DHEA are dangerously low. Years of stress-induced chronic metabolic dysfunction will be the cause of such advanced damage to the HPA axis.

Recovering from stage 3 is possible but often requires years of support and re-adaptation strategies so as to regain your resilience to stress and rebuild metabolic reserve to withstand new life challenges.

Hormone testing via saliva or the DUTCH test is the only way to diagnose HPA axis dysfunction (adrenal fatigue). It cannot be diagnosed via blood tests. Please see the section on hormone testing for more information regarding these tests.


Cortisol also known as the stress hormone is responsible for the production of Secretory Immunoglobulin A (sIgA) which is our first line of immune defence. When cortisol levels become affected then the ability of immune cells to produce adequate sIgA becomes compromised. This is the main reason we get sick so easily when under times of stress. Chronic stress down regulates the movement of sIgA into mucosal tissues of our airways and respiratory system making you more prone to pick up an infection.


Repair (Anabolic)

The repair/breakdown or anabolic/catabolic dynamic is what drives our health. It is one of the most crucial health principles to grasp.

We are constantly in a state of repair (anabolic) or breakdown (catabolic). Catabolism provides energy for all cells by breaking down large molecules such as protein and lipids into smaller molecules like amino acids and fatty acids. Being in an anabolic state means you are rebuilding, repairing, and literally re-constructing your body’s tissues. When you are anabolic your body is in constant regeneration, repairing blood vessels, heart tissue, rebuilding old bone and destroying cancer cells.

Growing children have a heavy bias towards anabolism until they reach adulthood.

Breakdown (Catabolic)

A stress induced catabolic state can be disastrous for our health. This breakdown or destructive phase occurs when breakdown outpaces repair. In a catabolic state you will break down muscle, bone, intestinal lining and other organs even your heart. This breakdown and destruction of health will ultimately lead tochronic disease.

A strong immune system can only exist when we spend more time in repair rather than breaking down. A healthy immune system will prevent the development of many chronic diseases, health comes from within after all. Prolonged immune system stress will lead your body to attack itself resulting in autoimmune diseases such as lupus, multiple sclerosis and rheumatoid arthritis.

Every day we have cancerous cells which are destroyed by our immune system so tumours don’t develop. Our blood vessels and heart require constant renewal to prevent plaque forming, the cause of cardiovascular disease. If the constant breaking down and repair of bone and joint tissue is disrupted osteoporosis and arthritis will occur.

When you’re suffering from HPA axis dysfunction or Adrenal Fatigue you will be in a catabolic state, bone loss occurs, muscle mass is lost and your gut lining and other organs will be broken down.

Hormone and Organic Acid testing can determine if you’re catabolic and in an inflamed, acidic state. This information allows you to address chronic degenerative diseases in their earliest stages, long before a pathological condition has developed.

Functional Medicine focusses on identifying and correcting the root cause of chronic disease not on treating or relieving symptoms.


Adrenal and Thyroid issues often arise together, their triggers can be identical and the treatment solutions will often overlap. Correcting adrenal dysfunction can either totally reverse thyroid insufficiency or help strengthen thyroid function when challenged by an autoimmune condition such as Hashimoto’s Thyroiditis.

Stress, inflammation, dietary factors, GI problems, high cortisol, insulin resistance and toxicity/liver problems can all cause damage to the thyroid gland.

Symptoms of thyroid dysfunction can often mimic signs of adrenal insufficiency;

  • Depression
  • Anxiety
  • Weight gain
  • Constipation
  • Hair loss
  • Sensitivity to temperature changes
  • Dry skin
  • PMS
  • Fibromyalgia
  • High cholesterol

Testing for thyroid hormones is best done via blood. It is extremely advisable to undergo a full thyroid panel which includes;

  • TSH
  • T3
  • T4
  • Reverse T3
  • Thyroid antibodies

Many providers will only test TSH which does not always give an accurate assessment of thyroid function.

Twenty percent (5 million people) of Australians have some type of thyroid disease and of that up to 15% or nearly 4 million people have an autoimmune thyroid disease such as Hashimoto’s Thyroiditis. Autoimmune disease is a group of disorders like Hashimoto’s, rheumatoid arthritis and Crohn’s disease. These autoimmune diseases often have their origin in the gut. When the digestive lining becomes damaged it becomes highly permeable often referred to as leaky gut. Undigested food, toxins and microbes more easily escape from the digestive system before they are broken down. Once in the bloodstream they can cause an allergic reaction and allow an autoimmune disease to develop. A compromised microbiome is another mechanism that can cause an autoimmune disease to take hold.


Serum (blood) testing is not an accurate way to measure the adrenal hormones as you will need to collect 4 samples over a 24 hour period, blood testing is obviously not suitable in this case. If you have had your cortisol levels measured via a blood test this will be a single test performed in the morning so it will not reflect the normal cortisol rhythm. Cortisol in the blood will also only be a reflection of the bound hormone which is inactive, the free or bioavailable levels need to be measured via urine or saliva. The DUTCH (Dried Urine Test for Comprehensive Hormones) test is the best measure for the adrenal hormones and can also assess sex hormones estrogen, progesterone and testosterone together with melatonin.­­­­­

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