HPA axis

Neuroendocrine circuit for stress: CRH (hypothalamus) → ACTH (anterior pituitary) → cortisol (adrenal cortex) with negative feedback on both hypothalamus and pituitary.

• Explains patterns in cortisol testing, responses to stress, and the physiology behind Cushing syndromes and adrenal insufficiency.

• Dexamethasone suppression testing workflows
• Early‑morning (8am) cortisol vs late‑night salivary cortisol
• Interpretation of ACTH values (high vs low) to localize pathology

1. Think in feedback loops: what is producing cortisol and who is driving it?
2. High cortisol + low ACTH → adrenal source or exogenous glucocorticoids
3. High cortisol + high ACTH → pituitary (Cushing disease) vs ectopic; use high‑dose dex or IPSS

1. HPA axis itself isn’t a disease—treat the underlying disorder (Cushing, Addison, exogenous steroids)
2. Stress‑dose steroids when physiologically suppressed axes are stressed (eg, surgery, sepsis)

• Random afternoon cortisol is rarely useful—use standardized morning/late‑night tests
• Chronic exogenous steroids suppress CRH/ACTH → adrenal atrophy → crisis risk

• Adrenal crisis: hypotension, hyponatremia, vomiting—give IV hydrocortisone immediately

1. Suspected hypercortisolism → screening test (overnight dex OR late‑night salivary OR 24‑hr urine)
2. If positive → ACTH level
3. High ACTH → pituitary vs ectopic (high‑dose dex ± IPSS); Low ACTH → adrenal imaging
4. Suspected adrenal insufficiency → 8am cortisol ± ACTH stimulation

• CRH stimulates ACTH from anterior pituitary; cortisol provides negative feedback
• High‑dose dex suppresses pituitary ACTH more than ectopic sources