The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the body’s stress response and is increasingly recognized as a contributor to a range of chronic health conditions. This review aims to provide an evidence-based overview of HPA axis dysregulation, including its underlying mechanisms, diagnostic approaches, and integrative treatment strategies.

A comprehensive review of peer-reviewed literature was conducted to examine the multifactorial contributors to HPA axis dysfunction. Sources included studies on psychological stress, dietary and lifestyle factors, genetic and epigenetic influences, immune system interactions, gut health, inflammation, environmental toxins, and hormonal imbalances. Diagnostic modalities such as serum and salivary cortisol testing were also reviewed.

HPA axis dysfunction is influenced by a complex interplay of internal and external stressors, including chronic psychological stress, dietary imbalances, disrupted circadian rhythms, and environmental exposures. Diagnostic methods vary in sensitivity and clinical utility, with diurnal salivary cortisol profiles offering insight into functional patterns. Integrative treatment approaches include patient-centered care, mind-body therapies, dietary and lifestyle interventions, targeted nutraceuticals, and adaptogenic herbs—each aimed at restoring balance and improving stress resilience.

Understanding HPA axis dysregulation through an integrative lens supports a more individualized and comprehensive approach to care. By bridging conventional endocrinology and functional medicine, clinicians are better equipped to address commonly overlooked symptoms such as fatigue, insomnia, mood disturbances, and poor stress tolerance, ultimately enhancing patient outcomes.