Allison Sayre, MSN, WHNP and Corey Schuler, PhD, FNP, CNS
Fatigue that doesn’t resolve with rest. Burnout that lingers long after the stressor has passed. A sense that the body no longer responds to pressure the way it once did. These experiences are often attributed to adrenal fatigue, yet this phrase oversimplifies what physiology actually reveals, and perhaps why it is widely considered an outdated term. A closer look at cortisol dysregulation tells a more nuanced and hopeful story.
Rather than pointing to adrenal failure, the evidence supports a model of stress adaptation, altered cortisol rhythms, and functional recalibration of the hypothalamic–pituitary–adrenal (HPA) axis. [1][2] From this perspective, the goal is not to fix cortisol, but to rebuild adrenal resilience.
Cortisol Rhythms: Why Timing and Pattern Matter More Than a Single Number
Cortisol is not meant to be constant. Under healthy conditions, it follows a daily rhythm that supports alertness and energy availability earlier in the day, then gradually declines to allow for rest and repair. This rhythm reflects an intact feedback system within the HPA axis, enabling cortisol to rise when stress requires it and fall when the demand passes. [1]
Cortisol also signals back to the brain, helping regulate its own production through negative feedback at the hypothalamic and pituitary levels. [1][3] This feedback is central to resilience. Cortisol dysregulation emerges when rhythmicity, responsiveness, or recovery becomes impaired, and this is often in ways that are not captured by a single resting measurement.
In this context, the most meaningful signal is frequently pattern and adaptability, not an isolated cortisol value.
Stress Adaptation and the HPA Axis
The HPA axis integrates physical, psychological, immune, and metabolic stress signals. Activation begins with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) secretion from the hypothalamus, followed by adrenocorticotropic hormone (ACTH) release from the pituitary and cortisol secretion from the adrenal glands. [1][4]
During acute stress, this system mobilizes energy and supports survival. Under chronic or repeated stress, however, the system adapts, and prolonged activation may lead to functional down-regulation of HPA axis signaling, resulting in reduced cortisol output or blunted responses to stimulation. [1][4]
Importantly, these changes occur without structural abnormalities of the adrenal glands or pituitary. In fact, research has shown in imaging studies show preserved adrenal size, reinforcing that cortisol dysregulation in stress-related conditions reflects functional recalibration rather than organ failure. [1]
High vs. Low Cortisol Symptoms: Patterns, Not Diagnoses
Cortisol dysregulation does not present uniformly. In earlier or more activated phases of stress exposure, individuals may experience symptoms often associated with higher cortisol output, such as heightened stress sensitivity, difficulty winding down, or disrupted sleep. These patterns reflect a system repeatedly mobilizing resources to meet ongoing demand. [1]
With sustained stress exposure, the HPA axis may recalibrate toward lower cortisol output or blunted responsiveness, a pattern frequently observed in chronic fatigue syndrome and fibromyalgia syndrome. This state is often experienced as persistent low energy, reduced stress tolerance, and difficulty sustaining effort. [1][3]
These descriptions represent physiological patterns, not diagnostic categories. Individuals may shift between them over time, or experience features of both. What unites these experiences is not cortisol excess or deficiency, but loss of adaptive flexibility.
Fatigue and Burnout as Signals of Adaptation
Fatigue in chronic stress states is not simply psychological or motivational. In stress-related conditions, fatigue correlates with altered HPA axis dynamics, particularly reduced ACTH or cortisol responsiveness during dynamic testing such as exercise, hypoglycemia, or pharmacologic stimulation. [1][3]
Baseline cortisol values often overlap between symptomatic individuals and healthy controls, limiting their diagnostic usefulness. [1] What differs is how effectively the system responds to challenge and recovers afterward. This helps explain why fatigue and burnout can feel profound even when routine laboratory testing appears normal.
From this perspective, burnout reflects a mismatch between ongoing demand and adaptive capacity, shaped by long-term stress signaling rather than acute hormone deficiency.
Adrenal Fatigue vs Adrenal Resilience
The concept of adrenal fatigue implies depleted or failing adrenal glands. The evidence reviewed by Tanriverdi and colleagues does not support this model. Instead, cortisol dysregulation in stress-related disorders occurs in the setting of intact endocrine structures and reflects altered regulation across the HPA axis. [1]
A more accurate framework is one of adrenal resilience, or the ability of the stress system to adapt, recalibrate, and protect itself under sustained demand. Resilience does not mean producing more cortisol or suppressing it. It means maintaining rhythmic signaling, appropriate responsiveness, and recovery after stress. [2]
Why “Fixing” Cortisol Misses the Bigger Picture
Efforts to fix cortisol by raising low levels or lowering high levels often overlook the complexity of HPA axis regulation. In reality, there is no single test, at present, that fully characterizes stress-system function, and oftentimes, static measurements poorly capture the dynamic process. [1][2]
Cortisol dysregulation reflects changes in central signaling, feedback sensitivity, hormone availability, and tissue responsiveness, and not a simple excess or deficiency. Treating cortisol as a number to correct risks pushing the system further from balance rather than restoring adaptive range.
Closing Perspective
Cortisol dysregulation helps explain why fatigue and burnout can persist even when conventional evaluations appear reassuring. The evidence suggests these states reflect functional adaptations of the stress system, not irreversible damage. [1] Reframing the conversation from adrenal fatigue to adrenal resilience shifts the goal from “fixing” cortisol to restoring adaptability. It recognizes that symptoms are not signs of failure, but signals of a system that has been working hard to protect the body under sustained demand, and that resilience, rooted in rhythmicity and flexibility, can be rebuilt.
Disclaimer:
The information provided is for educational purposes only. Consult your physician or healthcare practitioner if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
Allison Sayre, MSN, WHNP is a board-certified women’s health nurse practitioner with advanced expertise in hormonal health, integrative gynecology, and patient-centered care across the lifespan. She holds a Master of Science in Nursing and has served as both a clinical provider and educator in functional and conventional women’s health settings. At ARG, Allison contributes to medical education, clinical protocol development, and strategic content that supports the evolving needs of women's healthcare practitioners.
Corey Schuler, PhD, FNP, CNS has dedicated his career to advancing the science and clinical art of integrative medicine and serves as director of medical affairs for Allergy Research Group. He is a family nurse practitioner and practices holistic primary care at Synergy Family Physicians in White Bear Lake, Minnesota.