Research over the past 8 decades has emphasized the importance of the hypothalamic-pituitary-adrenal (HPA) axis and Cortisol regulation in modulating the endocrine, cardio- vascular, neurologic, and immune systems. Hypocortisolism, a relative or absolute state of paradoxically low cortisol, is emerging as an important yet incompletely understood mal- adaptive consequence of chronic stress exposure and HPA axis dysfunction. Many theories attempt to define the etiology through which hypocortisolism arises, yet none predominate due to the complex nature of the stress response and the dif- ficulty in proving definitive cause and effect.
Nonetheless, studies have shown a correlation between hypocortisolism and numerous disease states, such as meta- bolic syndrome, fibromyalgia, and chronic fatigue syndrome, as well as chronic pain syndromes, cardiometabolic disease, mood disorders, autoimmune diseases, and malignancies. The term adrenal fatigue has been proposed to describe a maladaptive state in which adrenal corticosteroid production