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.
Diagnosis & workup
Diagnostics & workup: - 24-hour urine free cortisol (elevated in Cushing syndrome) - Late-night salivary cortisol (loss of diurnal variation in Cushing) - Low-dose dexamethasone suppression test (1 mg overnight; failure to suppress cortisol <1.8 mcg/dL = Cushing) - Morning cortisol level (low in adrenal insufficiency; draw at 8 AM) - ACTH cosyntropin stimulation test (cortisol fails to rise in adrenal insufficiency) - Plasma ACTH level (high = primary adrenal insufficiency or ectopic ACTH; low = adrenal tumor or exogenous steroids) - Pituitary MRI if ACTH-dependent Cushing suspected - Adrenal CT if ACTH-independent Cushing suspected