Is it Adrenal Fatigue or HPA Axis Dysregulation?

For years, the term ‘adrenal fatigue’ has been used by many (myself included) in the functional health arena. It’s a term that’s been made very popular in the media as well, making it a near household term - so much so that many of our clients have self diagnosed this, reporting it as one of their conditions.

As with many areas of medicine, newer insights and research has caused a shift in our understanding of adrenal fatigue.

Typically, adrenal fatigue/adrenal exhaustion has been used to describe a state of extreme fatigue that’s precipitated by stress and resultant low cortisol levels.

However, the concept of adrenal fatigue just isn’t holding up to our new, current understanding of the stress response.

The adrenal fatigue theory posits that upon an initial stress response, cortisol and DHEA exist in a normal range. During Stage 1 adrenal fatigue, cortisol levels increase while DHEA decreases. Stage 2 and 3 reveal progressively diminishing levels of DHEA and cortisol until they are completely depleted in the 3rd stage. In the end, the adrenals are too fatigued to continue producing the hormones.

Really, it’s more complicated than this.

The central theme of adrenal fatigue it that the chronic stress response stays on, continually gassing the adrenal glands and eventually tiring them out.

The problem with this is that many people who have the symptoms of adrenal fatigue don’t actually have low levels of cortisol. There are studies looking at this - those with purported adrenal fatigue have normal or even elevated total levels of cortisol and cortisol metabolites (despite findings on diurnal cortisol test of low levels at one or more points in time).

Yet, I do want to be clear that despite this newer understanding, this doesn’t mean that people aren’t suffering from some type of dysregulation in which the adrenal glands do play a role, or that low cortisol is problematic for them.

What this new viewpoint will do is help us better understand and treat the same people (and it’s a lot of them!) using a more comprehensive approach.

What we now understand more clearly is that our stress response is governed by the hypothalmic-pituitary-adrenal (HPA) axis, hence the newly accepted term HPA axis dysfunction, rather than adrenal fatigue. The brain responds to stress before the adrenal glands do - they’re actually last in line.


The Hypothalamic-Pituitary Axis


The hypothalamus is a region of the brain that connects your autonomic nervous system (the part we don’t have to think about), the endocrine system (hormones) and the pituitary gland.

Think of your hypothalamus as the body’s thermostat in that it maintains homeostasis (balance) throughout the body by regulating hunger, thirst, temperature, sleep, etc.

The pituitary gland is a tiny, pea-size gland in the bottom of the front part of your skull. It’s often referred to as the “master gland” because it regulates all your endocrine (hormone) glands.

Lastly, the adrenal glands are just one of your endocrine organs. They’re located on top of the kidneys and produce several hormones other than just cortisol and DHEA including epinerphrine, norepinephrine, and aldosterone. These hormones play a role in fight or flight situations, blood pressure and fluid balance in the body, to name just a few.

Working together, the hypothalamus, pituitary and adrenal glands oversee your mood, motivation, immune system, energy levels and metabolism.

The HPA axis is a delicate symphony - each part working in sync with the other. One area of imbalance creates a ripple effect that can be felt throughout the body when it becomes desensitized to stress hormones.


When we experience stress, it activates the HPA axis which in turn activates numerous neuroendocrine (brain-hormone) signals that lead to the release of cortisol, epinephrine and norepinephrine - our body’s main ‘fight or flight’ hormones.

If we continue to experience stress and our HPA axis is chronically activated, our resilience and metabolic reserves become depleted. Put simply, we can no longer ‘take it’ - our ability to tolerate and deal with stressors, whether mental, emotional or physical is extremely limited.

When our metabolic reserves (the capacity of our body to adapt) are gone, you then typically see increased cortisol output, dysregulated cortisol rhythm (too much at night, too little in the morning), and imbalances in other HPA axis related hormones and neurotransmitters like pregnenalone, epinephrine, DHEA, melatonin, etc.

Hopefully you now understand why this isn’t just a cortisol deficiency because the adrenal glands have become ‘weakened’. It’s just that our ability to deal with the multiple modern stressors we experience is no match for our standard issue stress-response system.

When the HPA axis is impacted in this way, all other organs and systems are subject to imbalance as well - metabolism, gut, thyroid, brain, female and male reproductive systems, etc. These symptoms are typically diverse and far-reaching, and often mistaken for other clinical issues.


So, now what?

For starters, we need to look beyond just testing cortisol and DHEA when a person presents with symptoms consistent with adrenal fatigue (overwhelming fatigue, non-restorative sleep, intense sugar and caffeine cravings, and exercise intolerance (meaning it makes you feel worse and “hung over” after).

Only focusing/considering adrenal fatigue as a diagnosis is short sided and requires broader thinking.

I do however believe that cortisol and DHEA are important, but if what we’re really dealing with is HPA axis dysfunction, then we also need to look at other hormonal systems simultaneously (estrogen, progesterone, thyroid, markers of inflammation, food sensitivity, etc.) to gain a full picture of what’s going on.

Questions about this blog?

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In Health, Fitness and Endurance,


Dr. Jason Barker





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