Pathophysiology
Clinical meaning
Cortisol is the primary glucocorticoid produced by the adrenal cortex zona fasciculata, regulated by the hypothalamic-pituitary-adrenal (HPA) axis through negative feedback. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates anterior pituitary secretion of adrenocorticotropic hormone (ACTH), which in turn stimulates cortisol production. Cortisol exhibits a diurnal pattern: highest in early morning (6-8 AM) and lowest at midnight. Cushing syndrome results from chronic cortisol excess (exogenous steroids, pituitary adenoma, adrenal tumor, or ectopic ACTH). Adrenal insufficiency (Addison disease) results from cortisol deficiency. The diagnostic workup requires understanding of this axis to interpret test results correctly.