Adrenal Dysfunction and Fatigue: Cortisol + HPA Axis Dysfunction

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Exhaustion, insomnia, weight gain, and array of symptoms caused by chronically high-stress hormones have become known as adrenal dysfunction. These stress hormones are part of a larger, more complex system called the HPA axis. For a growing number of people, HPA axis dysfunction occurs as this system deteriorates in the face of high chronic stress.

Examining what causes adrenal insufficiency and adrenal disorders is the most crucial health information you need. Integrative medicine aims to restore balance to the HPA axis and relieve sufferers from puzzling, and often debilitating symptoms.


Adrenal Dysfunction

The HPA Axis Regulates Your Stress Response

First, it’s important to clarify that adrenal dysfunction is a common term used to describe symptoms that are now better understood as HPA axis dysfunction. HPA axis dysfunction involves dysregulation in the body’s stress response over time and is associated with numerous diseases.

Research shows that primary adrenal insufficiency occurs when your adrenal glands don’t make enough cortisol (1). Similarly, secondary adrenal insufficiency occurs when your pituitary gland doesn’t make enough ACTH, a hormone that controls your cortisol production (1).

The most common adrenal disorder is Addison’s Disease which causes fatigue, low blood pressure, weight loss, and a weak immune system (2). In fact, Addison’s can be a life-threatening situation and is referred to as an adrenal crisis. The acronym HPA stands for hypothalamic-pituitary-adrenal and involves:

Hypothalamus – Located in the brain and initiates a stress response, connecting your nervous system with your hormones via the pituitary gland.

Pituitary gland – Also located in the brain, the pituitary gland receives the message and releases messenger hormones.

Adrenal glands – The messenger hormones from the pituitary travel to the adrenal glands which sit atop the kidneys to create cortisol (and other hormones like adrenaline and some sex hormones).

This hormonal response is a beneficial and essential mechanism that occurs many times throughout the day. It helps to keep you alive and alert. A stress response isn’t always a bad thing. Although, chronic stress can lead to symptoms of adrenal fatigue or HPA axis dysfunction.

Support stress hormones with adaptogenic herbs in HPA Adapt.


Symptoms of Adrenal Dysfunction

The HPA axis’ most important role is to maintain homeostasis or the set of physiological circumstances that constantly adjust the body to keep us functioning optimally. This is a big job, as you can imagine. If any point in this system isn’t running smoothly, it can create a domino effect with each step affecting the rest.

Common symptoms of HPA axis dysfunction include:

Doctors have found HPA axis dysfunction in a high proportion of patients with chronic fatigue syndrome (CFS/ME), though the exact processes aren’t yet well understood (3).

Over time, exposure to chronic stress alters the way cortisol and other stress hormones communicate with the body. In a sense, the body becomes desensitized to stress hormones and we’re less able to return to a relaxed baseline (4).

Rather, stress hormones like cortisol are at the heart of HPA axis dysfunction, but also there is the body’s inability to regulate overall healthy stress response.

Read more: Holistic Tips to Handle Stress


Modern Stress Hormones and Adrenal Dysfunction

Chronic, unresolved stress is a key issue in the development of HPA axis or adrenal dysfunction. This can be emotional, physical, or mental stress, and comes in many forms.

When your mind experiences something it deems a threat, a series of physiological changes happen in the body to prime us to react–often called the fight-or-flight response. This reaction developed when humans were still doing things like running from predators or natural disasters.

Increases in alertness, heart rate, and blood flow to major organs help us, should we need to run away from a predator or protect our children or ourselves from a physical threat. Stress hormones also turn off things like immune function and reproductive function–two things that aren’t essential in a crisis (5).

Modern humans have very different threats now that this system wasn’t necessarily designed to handle. Our kids are wearing us out. Financial worries weigh heavy. An ability to perform at work all create demands that can exceed our ability to cope.

These threats last longer and aren’t usually physical in nature, which is actually more damaging and makes it harder for our nervous system to return to a resting state (6).


High Stress Means High Cortisol

The HPA axis controls your stress response. Your brain detects something stressful (i.e., an argument, a big presentation, even lack of sleep), sends out the message to ramp up cortisol, the threat generally passes, cortisol clears, and the body returns to baseline.

Well, that’s how it should work. Yet, when stress is chronic stress, this action never shuts off, and the adrenal glands secrete more and more cortisol.

Over time, your cells become “resistant” to cortisol, and the negative feedback system it relies on becomes ineffective. Lacking an intervention, the HPA axis no longer functions optimally. Over time, what was once high cortisol, can now result in cortisol levels that are too low (7).

This creates the hallmark symptoms of adrenal dysfunction–or HPA axis dysfunction.

Related: The Integrative Guide to Perimenopause


Testing Stress Hormones: Is There Adrenal Dysfunction?

It is difficult to assess adrenal fatigue or HPA axis dysfunction based on symptoms alone. As a result, it is important to determine levels of stress hormones and others before creating an optimal treatment plan. This begins with testing for adrenal fatigue through various hormone assessments.

Adrenal dysfunction testing may include:

  • DUTCH (Dried Urine Test for Comprehensive Hormones) to examine hormones and their metabolites
  • Saliva testing for DHEA and cortisol
  • ACTH stimulation test

The endocrine system is complex, and issues that arise are rarely a result of just one hormone. A hormone imbalance in one gland can cause an imbalance in other hormones as well.

Shop: DHEA and adrenal support


Integrative Medicine and Adrenal Dysfunction

Integrative and functional medicine seek to identify and treat the root causes of symptoms, rather than treating those symptoms on their own. Innovative diagnostics and personalized treatment plans give treatment for HPA axis dysfunction a discernible edge over conventional practices, which notoriously struggle with complex endocrine issues.


Expert Advice from an Integrative Medicine Team

Your CentreSpringMD doctor gets to know you and your medical journey by evaluating your history and risk factors. Then, we recommend diagnostic testing and develop a treatment plan tailored to address both your symptoms and holistic wellbeing.

In-Depth Testing and Diagnostics

Comprehensive lab work might include blood and saliva tests, nutrient deficiency assessment, and gut function analysis to give your integrative medicine team more insight into your individual chemistry.


Treating Adrenal Dysfunction and High Cortisol

Chronically high-stress hormones can lead to a complex issue known as HPA axis dysfunction, commonly referred to as adrenal fatigue. An inability for the nervous system to regulate stress hormones like cortisol can place you at risk for numerous diseases, and create debilitating symptoms like fatigue, insomnia, and weight gain.

Integrative medicine can restore balance to your body’s stress response with a personalized plan to address diet patterns, lifestyle modifications, supplements, and other targeted therapies.

An integrative healthcare provider at CSMD will give you a personalized adrenal dysfunction plan. This includes support from diverse modalities such as diet, lifestyle, supplements, and if appropriate, medications.

Book an appointment today with an expert integrative medical doctor at CSMD.



  1. https://www.hopkinsmedicine.org/health/conditions-and-diseases/underactive-adrenal-glands–addisons-disease
  2. https://www.mayoclinic.org/diseases-conditions/addisons-disease/symptoms-causes/syc-20350293
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045534/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181830/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361287/
  6. https://pubmed.ncbi.nlm.nih.gov/30229371/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465119/


adrenal fatigue, adrenals, cortisol, HPA, HPA Axis, Stress Management

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