Adrenal Fatigue (HPA Axis Dysfunction)
Naturopathic Support

What is adrenal fatigue – and what is HPA axis dysfunction?

Despite the name, adrenal fatigue doesn’t mean your adrenal glands have become tired or simply run out of cortisol.

In fact, “adrenal fatigue” isn’t recognised as a medical diagnosis. A more accurate way of describing the physiology behind many of these symptoms is HPA axis dysfunction (hypothalamic-pituitary-adrenal axis dysfunction), or changes in the way the body’s stress-response system is regulated.

I use the term adrenal fatigue on this page because it’s the language many women know and search for. But when we’re talking about what’s actually happening in the body, the HPA axis gives us a much more useful framework.

The HPA axis is the communication network between your brain, pituitary gland and adrenal glands. Your adrenal glands don’t simply decide how much cortisol to produce – they respond to signals coming from higher up this pathway, while cortisol feeds information back to the brain to help regulate the response.

With prolonged or repeated physiological stress, regulation across this system can change. This can affect cortisol rhythms, feedback signalling and how strongly the body responds to additional stress. So rather than thinking of the adrenal glands as “exhausted”, I think of it as a stress-response system that is no longer adapting as effectively as it once did.

And stress in this context doesn’t just mean feeling emotionally stressed. Poor sleep, chronic pain, inflammation, illness, under-fuelling, hormonal changes, surgery and prolonged emotional stress can all place demands on the same system.

This distinction matters because it changes the question from “How do I stimulate my adrenal glands?” to “What is placing demand on my stress-response system, and why isn’t my body adapting to it as well as it used to?”

What are the symptoms of adrenal fatigue and HPA axis dysfunction?

The symptoms commonly associated with adrenal fatigue can look very different from one woman to another, and fatigue is often only one part of the picture.

Some women struggle to get out of bed in the morning and feel as though they don’t properly come alive until later in the day. Others function reasonably well while they’re busy, only to crash as soon as they stop. You may feel exhausted but wired at night, increasingly unable to cope with stress, or notice that exercise, poor sleep or a busy week now takes much longer to recover from.

Common symptoms can include:

• persistent fatigue or waking unrefreshed
• difficulty getting going in the morning
• mid-morning or afternoon energy crashes
• feeling tired but wired at night
• poor stress tolerance or feeling easily overwhelmed
• anxiety, irritability or feeling on edge
• disrupted sleep or waking during the night
• brain fog and difficulty concentrating
• dizziness or light-headedness
• heart palpitations or adrenaline surges
• shakiness or feeling worse when meals are delayed
• exercise intolerance or prolonged recovery after activity
• increased sensitivity to caffeine, alcohol, medications or supplements
• hormonal or menstrual changes
• reduced resilience after illness, stress or poor sleep

Many of these symptoms are non-specific and can also occur with thyroid disorders, iron deficiency, sleep disorders, hormonal conditions, infections and other medical problems. This is why symptoms need to be considered within the broader clinical picture rather than used to diagnose adrenal fatigue or HPA axis dysfunction on their own.

High cortisol vs low cortisol: HPA axis dysfunction isn’t always the same pattern

HPA axis dysfunction doesn’t necessarily mean cortisol is simply “low”.

Some women may experience higher cortisol activity at certain times, while others may show a flatter daily pattern, a less pronounced morning rise or lower cortisol output at particular points across the day. Sometimes the pattern is mixed.

You might struggle with very low energy on waking, feel somewhat better once you’re moving, crash again in the afternoon and then experience a strange second wind at night. This is why looking at cortisol as simply “high” or “low” can miss what’s happening across the day.

Cortisol patterns also don’t exist in isolation. Sleep, circadian rhythm, blood sugar, illness, inflammation, exercise and psychological stress can all influence HPA-axis activity.

The more useful question is often not “is my cortisol high or low?” but “how effectively is my cortisol rhythm and broader stress-response system adapting to the demands being placed on my body?

What can contribute to adrenal fatigue and HPA axis dysfunction?

HPA axis dysfunction rarely comes down to simply being “too stressed”.

For many women, symptoms develop against a background of multiple physical, hormonal and emotional demands occurring over months or years.

These stressors can look very different from one woman to another and may include:

• chronic psychological or emotional stress
• poor or disrupted sleep
• chronic pain
• inflammation or autoimmune conditions
• endometriosis or adenomyosis
• chronic or significant infections
• mould or other environmental exposures
• blood sugar instability or under-fuelling
• nutrient deficiencies
• overtraining or inadequate exercise recovery
• hormonal changes, including perimenopause
• pregnancy or the postpartum period
• fertility treatment
• surgery, illness or significant physical trauma

Often, there isn’t one single contributor. It’s the accumulation that matters.

This is why two women can experience very similar adrenal fatigue symptoms while having very different underlying drivers. Understanding what may be placing ongoing demand on the HPA axis and broader stress-response system is often more useful than simply trying to “support the adrenals”.

Why standard cortisol testing doesn’t always explain adrenal fatigue symptoms

Cortisol is often described as the “stress hormone”, but it does much more. It helps you wake up and mobilise energy, supports blood sugar and blood pressure, and helps regulate immune activity and inflammation.

Cortisol also follows a daily rhythm, typically rising around waking and gradually declining towards night. This rhythm is one reason a single blood test doesn’t always tell the whole story.

A standard serum cortisol test measures cortisol at one point in time and is important for investigating conditions such as Addison’s disease, adrenal insufficiency and Cushing’s syndrome. However, a result within the laboratory range doesn’t necessarily show how cortisol is behaving across the rest of the day.

For example, morning cortisol may appear normal while testing across multiple time points reveals a flatter daily rhythm or altered cortisol awakening response. The blood test isn’t “wrong” – it’s simply answering a different question.

When clinically appropriate, salivary or urinary testing across the day can provide additional information about cortisol patterns. I interpret this alongside your symptoms, sleep, energy and broader clinical picture rather than relying on any single result in isolation.

How HPA axis dysfunction can affect your hormones

The HPA axis and reproductive hormone system are closely connected. When the body is under ongoing physiological stress, signalling between the stress-response and reproductive systems can change, potentially influencing ovulation, menstrual cycles and reproductive hormone production.

This is why some women notice hormonal changes alongside HPA axis dysfunction. Periods may become less predictable, PMS can worsen, ovulation may become less consistent, or fertility and other hormonal symptoms may become more noticeable.

Progesterone can be particularly affected because its production depends on ovulation. When ovulation becomes less consistent, progesterone production can also become less reliable, potentially contributing to symptoms such as anxiety, poor sleep, breast tenderness, irritability and worsening PMS.

These changes rarely occur in isolation. Poor sleep, under-fuelling, inflammation, illness, blood sugar instability and other forms of physiological stress can influence both the HPA axis and reproductive function.

This is one reason looking only at reproductive hormones doesn’t always explain the whole picture.

Why HPA axis dysfunction can feel worse during perimenopause

Perimenopause and HPA axis dysfunction can look remarkably similar. Fatigue, anxiety, disrupted sleep, brain fog, reduced stress tolerance, blood sugar changes and slower recovery can occur with both, making it difficult to know what’s actually driving your symptoms.

During perimenopause, fluctuating oestrogen and progesterone can influence sleep, mood, nervous system regulation and metabolic health. At the same time, existing HPA axis dysfunction may make it harder to adapt to these hormonal changes.

This can help explain why some women feel as though they’ve suddenly “hit a wall” in their forties. Perimenopause may not be the sole cause, but it can add another layer to an already strained stress-response system.

Often, it’s not one or the other. Hormonal changes and HPA axis dysfunction can overlap and influence many of the same systems.

Understanding what’s contributing to your symptoms matters because the approach may be different. If everything is attributed to perimenopause, other physiological stressors may be missed – while assuming everything is “adrenal” can mean reproductive hormone changes aren’t appropriately addressed.

Why immune, histamine and thyroid symptoms can overlap with HPA axis dysfunction

You may notice that fatigue isn’t the only thing that’s changed.

Perhaps you’re picking up every cold going around, taking longer to recover when you get sick, suddenly reacting to foods or alcohol you previously tolerated, or experiencing more headaches, congestion, flushing or digestive symptoms. You may even feel as though your thyroid symptoms have worsened at the same time.

These symptoms can seem unrelated, but the systems involved don’t operate independently.

Cortisol plays an important role in regulating immune activity and inflammation, while illness and inflammation themselves place additional demand on the HPA axis. This can create a two-way relationship where being unwell challenges the stress-response system, while altered HPA-axis signalling may influence how the body regulates immune and inflammatory responses.

Histamine is part of this picture too. Mast cells, histamine, the nervous system and stress-response pathways communicate with one another, which may help explain why some women notice their histamine symptoms become more reactive during periods of illness, poor sleep or significant physiological stress.

Thyroid symptoms can be particularly difficult to separate because there is so much overlap. Fatigue, brain fog, feeling cold, low mood, poor exercise tolerance and slow recovery can occur with both thyroid dysfunction and HPA-axis-related symptoms.

This doesn’t mean HPA axis dysfunction causes recurrent infections, histamine intolerance or thyroid disease. But when several of these symptoms appear together, it can be a clue that there is more than one piece of the puzzle – and that looking at each system in isolation may not explain the whole story.

The connection between HPA axis dysfunction, dysautonomia and POTS

If you experience dizziness, heart palpitations, feeling faint, heat intolerance or feeling significantly worse when standing, there may be more going on than HPA axis dysfunction alone.

The HPA axis and autonomic nervous system work closely together to help your body adapt to physical stress. Cortisol helps support blood pressure and the responsiveness of blood vessels to adrenaline and noradrenaline, while these stress hormones help regulate heart rate and circulation when your body needs to compensate.

This connection can become particularly noticeable when you stand. Your body needs to quickly adjust heart rate and blood vessel tone to maintain blood flow to the brain. If autonomic regulation isn’t working efficiently, greater sympathetic and adrenaline activity may be needed to compensate, contributing to palpitations, shakiness, dizziness or an anxious, “wired” feeling even when you’re physically exhausted.

For some women, these symptoms reflect orthostatic intolerance, while others may be diagnosed with a recognised form of dysautonomia such as postural orthostatic tachycardia syndrome (POTS). HPA axis dysfunction doesn’t cause POTS, but disturbances in stress-response and autonomic regulation can occur alongside one another and produce overlapping symptoms.

Heat and high humidity can make symptoms worse by dilating blood vessels and placing greater demands on circulation. Dehydration, prolonged standing, inadequate food intake, illness and poor sleep can also reduce tolerance, while some people report worsening symptoms with changes in barometric pressure.

Persistent dizziness, fainting, significant palpitations or marked exercise intolerance shouldn’t simply be attributed to cortisol or HPA axis dysfunction. POTS and other forms of dysautonomia are distinct conditions that require appropriate medical assessment.

When these symptoms occur alongside fatigue and poor stress tolerance, looking at cortisol alone may therefore miss an important part of the picture.

Why HPA axis dysfunction can cause night waking, anxiety and feeling “tired but wired”

One of the most confusing experiences with HPA axis dysfunction is feeling completely exhausted while your body still seems unable to switch off.

You might struggle through the day with very little energy, only to feel strangely alert at night. Or you may fall asleep easily but wake in the early hours feeling anxious, restless, hot or suddenly wide awake.

This “tired but wired” pattern can make more sense when you look beyond energy alone. Cortisol follows a circadian rhythm, while adrenaline and the nervous system help the body respond to changing demands throughout the day. When these systems aren’t coordinating effectively, the transition between daytime activation and night-time recovery may become more difficult.

Blood sugar instability can add another layer, particularly overnight, while pain, inflammation, hormonal changes and ongoing nervous system activation can make restorative sleep harder to achieve.

This is why low energy doesn’t always equal sleepiness. You can feel physically depleted while parts of the stress-response system remain activated, creating the frustrating combination of fatigue, anxiety, restless sleep and feeling simultaneously exhausted and overstimulated.

The connection between HPA axis dysfunction, cortisol and blood sugar

You might wake feeling weak, nauseous or completely depleted but strangely have no appetite. Perhaps you crash mid-afternoon, become shaky or anxious when you haven’t eaten, or wake in the early hours feeling suddenly alert, hot or with your heart racing.

Blood sugar can be an important part of this pattern.

Cortisol and blood sugar work closely together throughout the day. Between meals and overnight, when glucose from food isn’t readily available, cortisol works alongside hormones such as glucagon and adrenaline to help maintain enough glucose for your brain and body.

When HPA axis and cortisol regulation are disrupted, these periods without food may become harder to tolerate. This can be particularly noticeable first thing in the morning after an overnight fast, during an afternoon energy slump, or overnight when you’ve gone several hours without eating.

If blood glucose falls sufficiently during the night, the body can release counter-regulatory hormones, including adrenaline and cortisol, to help bring it back up. That response may contribute to waking suddenly feeling anxious, shaky, hot or with a racing heart.

It can also become a cycle. Poor sleep can make blood sugar regulation more difficult the following day, while skipping meals, fasting or under-eating can place additional demand on an already struggling stress-response system.

This is why I pay close attention to meal timing and adequate nutrition in women with HPA-axis-related symptoms. Regular meals containing protein, healthy fats, fibre and appropriate carbohydrates can help provide more consistent energy and reduce the need for repeated stress-hormone responses between meals.

HPA axis dysfunction, exercise intolerance and slow recovery

One of the more frustrating changes with HPA axis dysfunction is that exercise that once made you feel better can start leaving you depleted.

You may tolerate the activity itself reasonably well, only to crash later that day or the following day. Recovery takes longer, energy drops, sleep can worsen, and pushing through can sometimes leave you feeling more wired rather than pleasantly tired.

Exercise is itself a physiological stressor. Cortisol, adrenaline, glucose regulation, cardiovascular function and the nervous system all contribute to meeting the increased energy demands of physical activity and recovering afterwards.

So when someone is already struggling with poor sleep, inadequate energy availability, illness, pain, autonomic symptoms or other physiological stressors, their tolerance for exercise may be very different from what it once was.

This doesn’t mean exercise should necessarily be avoided. It means the type, intensity and duration may need to match your current capacity. For some women, rebuilding tolerance gradually is more helpful than continually pushing through exhaustion.

Rest still matters, but rest alone may not resolve the underlying pattern if other physiological stressors continue placing demands on the body.

Why supplements can suddenly feel too stimulating

One pattern I often see in women experiencing HPA-axis-related symptoms is: “I used to tolerate supplements really well, but now I seem to react to everything.”

When the stress-response and nervous systems have become particularly reactive, stimulating supplements can sometimes feel like too much. Adaptogens, caffeine or nutrients intended to support energy may leave some women feeling anxious, shaky, overstimulated, unable to sleep or noticeably more “wired”.

This is why adrenal support isn’t necessarily about stimulating the adrenal glands or trying to increase cortisol.

For someone who has become particularly sensitive, I generally prefer to start low, introduce one thing at a time and consider the foundations that may be keeping the stress-response system under pressure, including sleep, nutrition, blood sugar regulation and nervous system function.