What role does Cortisol play in fatigue?

Cortisol, the primary stress hormone, is secreted by the adrenal cortex and follows a circadian rhythm. In chronic stress or dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, cortisol levels can be either elevated or lowered, both linked to fatigue. Persistently high cortisol disrupts sleep, promotes inflammation, and can contribute to burnout-like symptoms. Low cortisol (adrenal insufficiency) conversely leads to exhaustion, lack of drive, and circulatory issues. Evidence for these associations comes from clinical practice and physiological studies, but the predictive power of a single cortisol measurement (e.g., in saliva or blood) is limited due to many confounding factors like time of day, diet, and acute stress. Genetic testing for cortisol-related genes (e.g., NR3C1, FKBP5) provides only mechanistic hints, not clinically actionable results. For persistent fatigue, a medical workup (e.g., diurnal profile, dexamethasone suppression test) is recommended before acting on direct-to-consumer tests. The provided context does not contain specific information on cortisol and fatigue, so this answer is based on general medical knowledge.