Clinical meaning
The hypothalamic-pituitary-adrenal (HPA) axis is the primary neuroendocrine stress response system. Physical or psychological stress activates paraventricular nucleus neurons in the hypothalamus to release corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). CRH stimulates corticotroph cells in the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH acts on the zona fasciculata of the adrenal cortex to produce cortisol. Cortisol exerts widespread metabolic effects: gluconeogenesis (raising blood glucose), protein catabolism (muscle wasting), lipolysis (redistribution of fat), anti-inflammatory and immunosuppressive effects, and maintenance of vascular tone. Cortisol feeds back negatively on the hypothalamus and pituitary to terminate the stress response. Chronic stress disrupts this feedback, leading to sustained cortisol elevation, hippocampal neuronal damage (impairing memory), immunosuppression, metabolic syndrome, and cardiovascular disease. The clinician must recognize the clinical consequences of chronic HPA axis dysregulation.
Diagnosis & workup
Diagnostics & workup: - 24-hour urinary free cortisol (UFC) for suspected Cushing syndrome - Late-night salivary cortisol (elevated in Cushing - loss of diurnal rhythm) - 1mg overnight dexamethasone suppression test (cortisol > 50 nmol/L = non-suppression) - Morning serum cortisol and ACTH (low cortisol + low ACTH = secondary adrenal insufficiency) - ACTH stimulation test (cosyntropin 250 mcg IV - cortisol should rise > 500 nmol/L) - Screen for metabolic consequences: fasting glucose, HbA1c, lipid panel, BMI