As healthcare professionals, we are acutely aware of the critical role the endocrine system plays in systemic regulation. Yet, the adrenal glands—despite their relatively small size—are often underappreciated for their expansive physiological influence. Perched on top of each kidney, these glands are central to the body’s response to stress, metabolic regulation, immune modulation, and neuroendocrine communication.
In clinical practice, recognising patterns of adrenal dysregulation and understanding how to support adrenal function can significantly impact patient outcomes, particularly in those with chronic stress, fatigue, or neuroendocrine imbalances.
Anatomy and Function of the Adrenal Glands
Each adrenal gland comprises two anatomically and functionally distinct regions:
- Adrenal Cortex: Produces glucocorticoids (cortisol), mineralocorticoids (aldosterone), and androgens (e.g., DHEA).
- Adrenal Medulla: Releases catecholamines (adrenaline and noradrenaline) as part of the acute stress (fight-or-flight) response.
These hormones influence blood pressure, fluid and electrolyte balance, glucose metabolism, immune function, and neurocognitive health.
Re-framing “Adrenal Fatigue”: Functional Dysregulation vs. Structural Disease
While “adrenal fatigue” remains a controversial and unrecognised diagnosis in conventional endocrinology, many integrative and functional medicine practitioners observe clinically relevant patterns of HPA axis dysregulation. Rather than implying glandular insufficiency (as in Addison’s disease), this refers to maladaptive neuroendocrine signalling in response to chronic stress.
Patients may present with:
- Persistent fatigue, especially morning fatigue
- Sleep-wake dysregulation
- Cognitive sluggishness (“brain fog”)
- Cravings for sodium or sugar
- Mood lability or depressive symptoms
Emerging literature also supports the concept of adrenal senescence, characterised by an age-associated decline in DHEA and alterations in diurnal cortisol rhythms. These changes are associated with cognitive decline, sarcopenia, and mood disorders.
Understanding Stress and the HPA Axis
The hypothalamic-pituitary-adrenal (HPA) axis orchestrates the body’s response to physical and psychological stress. Chronic activation can lead to axis dysregulation—manifesting as either hypercortisolemia (initially) or hypocortisolism (in later stages), depending on chronicity and individual resilience.
A helpful model is the N.U.T.S. acronym:
- Novelty
- Unpredictability
- Threat to the ego
- Sense of control (or lack thereof)
These psychosocial stressors increase allostatic load, taxing the HPA axis and predisposing individuals to metabolic, immune, and neuropsychiatric sequelae.
Neuroendocrine Impacts: Cortisol and Brain Function
The hippocampus, amygdala, and prefrontal cortex are rich in glucocorticoid receptors, and cortisol modulates memory, emotional processing, and executive function. Both insufficient and excessive cortisol can impair these processes, while optimal diurnal cortisol rhythm supports learning and affect regulation.
Nutritional and Lifestyle Considerations for Adrenal Support
A foundational approach to supporting adrenal and HPA axis health includes:
- Macronutrient balance: Regular intake of protein and complex carbohydrates helps stabilise blood glucose and cortisol dynamics.
- Micronutrients:
- Vitamin C and B-complex vitamins: Essential co-factors in adrenal hormone synthesis.
- Magnesium: Modulates the stress response and supports neuroendocrine function.
- Omega-3 fatty acids: Exhibit anti-inflammatory properties and may modulate HPA axis activity.
- Antioxidants: Combat oxidative stress secondary to elevated cortisol.
- Hydration and electrolyte balance: Crucial, especially in patients with low aldosterone activity.
Minimising consumption of refined sugars and highly processed foods helps prevent insulin resistance and systemic inflammation, both of which further stress the adrenal system.
Chronobiology: Light Exposure and Cortisol Regulation
Light entrainment is vital to maintaining a healthy cortisol awakening response (CAR). Morning exposure to natural light supports the circadian rhythm, while excessive evening light—particularly blue light—can suppress melatonin and dysregulate cortisol.
Clinical recommendations:
- Encourage consistent sleep-wake cycles.
- Limit screen exposure 1–2 hours before bedtime.
- Incorporate morning outdoor activity when feasible.
Adaptogens and Botanical Support
Several adaptogenic herbs have shown promise in modulating the stress response and supporting HPA axis balance:
- Ashwagandha (Withania somnifera): Reduces cortisol and improves stress resilience.
- Rhodiola rosea: Enhances cognitive function under stress and may modulate cortisol release.
- Holy Basil (Ocimum sanctum), Eleuthero (Siberian ginseng), Maca, and Licorice root: Offer variable support for adrenal tone and hormonal balance.
Standardised extracts and clinical dosing are important to ensure efficacy and safety, particularly in patients on concurrent medications.
Functional Testing: Salivary Cortisol and DHEA Panels
While serum cortisol remains useful for diagnosing overt adrenal pathology, salivary testing provides a more nuanced, diurnal perspective. Multi-point salivary cortisol (e.g., upon waking, 30 minutes post-waking, midday, and evening) can reveal blunted CAR, flatlined curves, or inverted rhythms—offering actionable insights for treatment.
In some cases, DHEA-sulfate measurement (salivary or serum) provides further context regarding anabolic-catabolic balance and aging-related decline.
Conclusion: A Systems Approach to Adrenal Health
As clinicians, we are in a unique position to identify early signs of HPA axis dysregulation and implement targeted interventions. By combining clinical acumen with evidence-informed tools—ranging from nutrition and botanicals to circadian hygiene and functional testing—we can help patients restore physiological resilience.
Supporting adrenal health is not simply about addressing fatigue; it’s about optimising the body’s adaptive capacity in a world of chronic stress.