Is adrenal fatigue real? Explaining HPA axis dysfunction

If you’ve googled your symptoms (like the best of us) and searched something like ‘always tired and hungry’ you might have come across the term ‘adrenal fatigue’.

Adrenal fatigue is a term that has gained popularity in complementary medicine, but the Endocrine Society states there’s no scientific proof for the condition.

Those who believe in adrenal fatigue think that chronic stress tires out the adrenal glands which play a vital role during the stress response, causing a specific group of symptoms which collectively are called ‘adrenal fatigue’. Symptoms of adrenal fatigue include chronic fatigue, problems falling asleep and waking up, cravings for salty or sweet food and weight gain.

In her article, Doctor Melinda Ring explains that HPA axis dysfunction is the ‘more accurate descriptor of the impact of chronic stress on the body vs the term “adrenal fatigue”’.

What is HPA axis dysfunction?

The HPA axis (hypothalamic-pituitary-adrenal axis) governs your stress response. Your adrenals produce cortisol and other hormones known as glucocorticoids. Nearly every cell in your body has a glucocorticoid receptor, which means that cortisol has wide-ranging effects, and is able to affect every organ – from that twist in your tummy before presenting at work, to anxious thoughts that whirl before sleep.

HPA axis dysfunction means you have a narrow window of tolerance in response to stress. The ‘window of tolerance’ is a term coined by Professor Dan Siegel, in which people can function well and emotionally regulate effectively.

“Almost 100% of patients I see have HPA axis dysfunction – which includes the teenagers,” says IMI naturopathic doctor Benita Perch. “In Hong Kong we’re all exposed to stress, even young people. It’s a very stressful world and I don’t think anyone lives a balanced life in Hong Kong.”

When faced with a stressor you might enter a state of hyperarousal (above your window of tolerance) in which you’re more reactive, in fight or flight, possibly angry or anxious. Or, you might enter hypoarousal (below your window of tolerance) in which you freeze, become unresponsive, depressed or rigid about your boundaries. Having a narrow window of tolerance can make it hard to bounce back after experiencing a stressful situation.

There are two stages of HPA axis dysfunction. The first is hyperactivity, during which cortisol levels are raised, and your sympathetic nervous system is stimulated (fight or flight). This leads to symptoms like anxiety, sleeping problems, high blood pressure and weight gain (cortisol stimulates appetite and causes the body to store fat).

In contrast, the second phase is defined by hypoactivity and low cortisol levels. The freeze response during this phase is typical – in the animal kingdom, this might look like playing dead. In the human world, it looks more like being unable to get out of bed, or disassociating in a meeting. In this phase, you might experience fatigue, depression, low blood pressure, poor immunity and an inability to manage stress.

“People often tell me they’re not stressed. But what they mean is they’re not anxious. You can be very stressed, even if it doesn’t translate to anxiety. Usually, the life you’re living is stressful by nature – you have to get up early, get your kids to school, go to work, then you’re coming home, your evenings are busy and the cycle repeats. When I test clients’ cortisol levels, they’re often shocked when they see how off-base their levels are. They think they’re not stressed, but they’re working a lot, running marathons, going to HIIT classes. It’s a question of how much mental and physical load they have,” says Dr Benita.

Diagnosing HPA axis dysfunction

HPA axis dysfunction, thyroid conditions, iron imbalances and autoimmune conditions all share similar symptoms.

“You may notice HPA axis dysfunction because you’re experiencing sleeping problems – struggling to sleep, waking up in the night, or waking up early and experiencing anxiety. That tired but wired feeling is typical. Or your sleep might be fine, but you’re exhausted, for no tangible reason,” says Dr Benita. “In these instances we check iron levels, thyroid health and cortisol levels, which defines whether you’re experiencing HPA axis dysfunction, or something else.”

Typically, cortisol peaks around the time you wake, and is at its lowest before bedtime. Higher cortisol levels at bedtime suggest you may have an overactive HPA axis (the first stage of dysfunction). Other signs of dysregulation include abnormal cortisol awakening responses and a flatter cortisol pattern throughout the day.

Emotional stress and HPA dysfunction

Mental health plays a big role. Major risk factors for HPA axis dysregulation include adverse childhood experiences and a history of trauma.

“Trauma is not just a story - it’s somatic. It lives in the body. Often, when you experience trauma, your defences are high, and the trauma gets held in the nervous system and the body,” explains IMI Mindfulness psychotherapist, Carole Bradshaw. 

A 2010 study shows that those experiencing enhanced suppression of cortisol, the second phase of HPA axis dysfunction (freeze) tend to have higher scores in compulsive behaviour, anxiety and avoidant coping strategies - think doomscrolling, or using substances like drugs, alcohol or nicotine to try to numb. 

These coping strategies add to mental health problems, worsening anxiety and depression, which are both symptoms of and causes of HPA axis dysfunction.
So which coping strategies actually help? “Trauma informed approaches are bottom-up, which means they regulate through awareness of bodily experiences and rebalancing your nervous system, rather than something like CBT, which is an example of top-down, in which you work through the mind first,” says Carole. 

“Calming breath practices can help, especially in, or looking at nature. When nature isn’t easily accessible, taking a walk and really focusing on the contact between your feet and the ground can help you reconnect with your body and the present moment. Humming is also great, as this activates your vagus nerve and parasympathetic nervous system and lowers your heart rate. It’s a simple, powerful practice that helps ease anxiety and is especially useful right before sleep,” she adds.

Nutritional factors and HPA dysfunction

Nutritional imbalances in B vitamins, magnesium, zinc and omega 3s are all essential for the healthy function of the HPA axis. Healthy dietary choices help manage stress, while those high in sugar and fat can disrupt the hormones involved in regulating your stress response.

Your gut is pivotal for emotional wellbeing, and your gut-brain axis communicates with the HPA axis. “Cortisol has a massive effect on the gut. A lot of digestive issues are stress related,” says Benita.

Gut microbes can activate the HPA axis and gut bacteria release neurotransmitters which interact with your nervous system. Likewise, HPA activation can affect gut microbes, and the permeability of your gut which can lead to leaky gut. Common friendly gut bacteria like Lactobacillus and Bifidobacterium have been shown to heal HPA axis dysfunction.

Interestingly, studies on pregnant women showed that those who had experienced traumatic events in childhood had higher levels of bad bacteria, demonstrating the link between the gut and mental health.

Physical stress and HPA dysfunction

Not only does emotional stress cause HPA axis dysfunction, physical stress can too. One of the biggest pressures on physical health in Hong Kong is the effect of pollution, which causes oxidative stress. Studies show that girls exposed to higher levels of air pollution have higher levels of anxiety, and a more heightened HPA response.

Over-exercising is also linked to HPA axis dysfunction. It’s important not to skip your rest days.

“A balanced approach to exercise depends on the structure of your life,” Benita says. “If you’re working 12 hour days and then running marathons or going to HIIT classes, it’s likely to impact your health. But if you’re someone who doesn’t work or has a more balanced life, that might be okay. I treat a lot of women and recommend weights twice a week, cardio twice a week and then some type of restful, yin exercise like yoga once or twice a week.”

Hormonal imbalances and thyroid health can affect HPA axis function. Higher levels of oestrogen can sensitise the HPA axis, leading to higher levels of cortisol when faced with a stressor. Testosterone often works in the opposite fashion, causing hyposensitivity to stress. An overactive thyroid can cause both high and low levels of cortisol, while an underactive thyroid tends to lead to high levels of cortisol.

Similar to mental health, poor sleep is both a symptom of and a cause of HPA axis dysfunction. Your circadian rhythm and HPA axis are connected. Sleeping problems, sleep quality and duration of sleep are factors in HPA axis dysregulation. Sleep inhibits the HPA axis, which is important when healing from a stressor or chronic stress. Likewise, activation of the HPA axis is associated with sleeping problems. 

Genetics and HPA dysfunction

And – in some instances, we can blame our parents. Many genetic variations increase our susceptibility to HPA dysfunction. When it comes to developing anxiety disorders, 30-50% can be attributed to inherited factors. A review by the University of Cambridge suggests that genetics related to the HPA axis play a role in the relationship between significant life events and depression.

The genes that affect HPA axis function include the CRHR1 gene, serotonergic genes like 5-HTTLPR and MAOA-LPR.

A variation of the MTHFR gene is associated with depression and HPA axis dysfunction, with research demonstrating its link to altered cortisol levels. COMT is another genetic variant associated with increased sensitivity to stress and HPA axis dysfunction. At IMI, we can test both MTHFR and COMT to assess if your genetics are playing a role.

The good news is that our genetics don’t have the final say over outcome, and controllable factors in our environment can help us regulate our HPA axis.

How can you regulate your HPA axis?

Dr Ring’s article reinforces what we at IMI have seen for decades. According to her, a bio-psycho-social-spiritual model is ‘well-suited’ to the task of tackling HPA dysfunction. This phenomenon is not just physical or mental. It’s the manifestation of many factors which feed into one another.

When people are treated for HPA axis dysfunction, Benefits says “People feel calmer, they have less anxiety and they sleep better. As a result of that, so many other symptoms get better. They’re happier.”

We recommend enriching your diet with nutrient-dense foods high in antioxidants, and eating at regular times, not too close to bedtime. Our naturopaths can help design a meal plan around your preferences and needs, like short prep time, to help heal HPA axis dysfunction.

They can refer you for tests to identify possible factors playing a role in dysfunction. This may include toxin levels, oxidative stress, nutritional imbalances, hormonal imbalances and gut health.

Based on your data, they’ll create a personalised treatment plan to heal areas of wellbeing contributing to HPA axis dysfunction and resolve any symptoms you’re experiencing – from fatigue to cravings and poor immunity. When needed, they may integrate other modalities into your treatment, like acupuncture or counselling.
Research has shown that acupuncture has a rebalancing effect on hormonal health, and a 2024 review demonstrated that acupuncture is a therapeutic intervention for HPA dysfunction.

Trauma informed psychotherapy and counselling provide a powerful way to heal HPA axis dysfunction when emotional factors are at play. “Safe, relational experience from a neurobiology perspective, is really important. Co-regulation is one of the most powerful ways to expand the window of tolerance,” says Carole.

Our psychologists and psychotherapists provide a confidential, non-judgemental space to discuss your thoughts and emotions.

 “Feeling your feelings, rather than suppressing them is also really important when it comes to expanding your window of tolerance. If you fear your emotions, your nervous system learns that your emotions equal danger. By working with them in a safe, regulated way, you can learn how to allow the emotion to rise up and pass. At the same time, your nervous system learns, I can feel emotions, and still be safe,” she adds.

You don’t have to start big when you begin therapy. You might simply want to start by talking about the impact of your fatigue – or perhaps there’s an event in your history that you’re ready to explore. Our practitioners work with trauma-informed approaches like somatic experiencing, sensory regulation, mindfulness and breathwork. These practices help bring more ease to your nervous system and expand your window of tolerance.

Our talk therapists work at your pace, allowing your process to unfold naturally. Getting support for issues affecting your mental and emotional health can help improve your sleep and break the cyclical relationship between mental health and HPA axis dysfunction.

References
M Ring, An integrative approach to HPA axis dysfunction: from recognition to recovery, 2025.
Endocrine Society, Adrenal Fatigue, 2022.
F A Cadegiani, C E Kater, Adrenal fatigue does not exist: a systematic review, 2016.
Zheng JY, Zhu J, Wang Y, Tian ZZ. Effects of acupuncture on hypothalamic–pituitary–adrenal axis: Current status and future perspectives., 2024.
O Karin et al, A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks, 2020
Manchester University, NHS Foundation Trust, Adverse childhood experiences (ACEs) and attachment
L Thau, Physiology, cortisol, 2023.
H Hori et al, Relationships between psychological distress, coping styles and HPA axis reactivity in healthy adults, 2010.
M Nikbakhtzadeh et al, Cross-talk between the HPA axis and addiction-related regions in stressful situations, 2023.
B Misiak et al, The HPA axis dysregulation in severe mental illness: can we shift the blame to gut microbiota?, 2020.
N Nader et al, Interactions of the circaidian CLOCK system and the HPA axis, 2010.
N C Nicolaides et al, HPA axis and sleep, 2020.
B Ferguson et al, Genetic load is associated with hypothalamic-pituitary-adrenal axis dysregulation in macaques, 2012.
C Norman and H N Buttenschon, Gene-environment interactions between HPA-axis genes and stressful life events in depression: a systematic review, 2019.
H Lindholm et al, Genetic risk-factors for anxiety in healthy individuals: polymorphisms in genes important for the HPA axis, 2020. 
J G Miller et al, Air pollution is associated with elevated HPA-axis response to stress in anxious adolescent girls, 2020. 
K V Hookenson et al, Child MTHFR C677T genotype and HPA stress regulation at 6 years of age, 2013. 
B L Hankin et al, Cortisol reactivity to stress among youth: stability over time and genetic variants for stress sensitivity, 2015.