Endocrinology
Stress Hormones
Cortisol and catecholamines — the body's response to threat
Acute stress activates two parallel systems. The sympathetic-adrenomedullary axis releases epinephrine and norepinephrine within seconds — increases heart rate, contractility, blood pressure, blood glucose, and bronchodilation; mobilizes fight-or-flight. The hypothalamic-pituitary-adrenal axis — CRH from hypothalamus, ACTH from anterior pituitary, cortisol from zona fasciculata — operates over minutes to hours. Cortisol mobilizes glucose via gluconeogenesis, breaks down protein and fat, suppresses immunity and inflammation, and amplifies catecholamine vascular effects (permissive action). Chronic activation drives visceral obesity, insulin resistance, hypertension, hippocampal atrophy, immunosuppression, sleep disruption. Stress disorders — Cushing syndrome (excess cortisol), Addison disease (insufficiency), pheochromocytoma (catecholamine tumor).
- Acute systemSympathetic-adrenal medulla; seconds
- Slow systemHPA axis; minutes to hours
- Cortisol normal AM5-25 µg/dL (138-690 nmol/L)
- Stress dose steroidsHydrocortisone 100 mg IV q8h
- CatecholaminesEpinephrine 80%, norepinephrine 20% from medulla
- Pheochromocytoma24-hr urine metanephrines or plasma free
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Why stress hormones matter
- Sepsis management. Norepinephrine is first-line vasopressor; hydrocortisone for refractory shock.
- Anaphylaxis. Epinephrine IM is first-line; do not delay.
- Steroid prescribing. Long-term effects mimic Cushing.
- Resistant hypertension. Screen for pheochromocytoma, primary aldosteronism, Cushing.
- Adrenal crisis. Recognize and treat empirically.
- Critical illness. Relative adrenal insufficiency in sepsis.
- Mental health. Chronic stress drives anxiety, depression, PTSD biology.
Common errors
- Beta blocker before alpha in pheochromocytoma. Unopposed alpha causes hypertensive crisis.
- Missing adrenal crisis as refractory shock. Empirical hydrocortisone 100 mg saves lives.
- Tapering chronic steroids too fast. HPA axis recovery takes weeks to months.
- Trusting random cortisol. Diurnal variation; use morning, midnight, or stim test.
- Stress-dosing minor procedures. Outpatient dental work usually doesn't need stress dose.
- Ignoring screening in resistant hypertension. Misses treatable secondary causes.
Frequently asked questions
How does cortisol respond to stress?
Hypothalamic CRH stimulates pituitary ACTH, which stimulates adrenal cortex to produce cortisol. Cortisol mobilizes glucose (gluconeogenesis from amino acids and glycerol), suppresses inflammation, suppresses immunity, raises blood pressure (permissive for catecholamines, mild mineralocorticoid effect), and provides negative feedback to suppress CRH and ACTH. Diurnal pattern — peak 6-8 AM, trough at midnight. Stress, surgery, illness, hypoglycemia override the rhythm. Persistent elevation drives metabolic syndrome.
What is Cushing syndrome?
Excess cortisol. Causes — exogenous steroids (most common), pituitary adenoma (Cushing disease, 70%), ectopic ACTH (small cell lung, carcinoid; very high ACTH and cortisol), adrenal adenoma or carcinoma (low ACTH). Features — central obesity, moon face, buffalo hump, purple striae, proximal muscle weakness, hypertension, hyperglycemia, osteoporosis, immunosuppression, depression. Diagnosis — 24-hr urinary free cortisol, late-night salivary cortisol, low-dose dex suppression. Localize with ACTH, high-dose dex, MRI, IPSS.
What is Addison disease?
Primary adrenal insufficiency. Autoimmune most common in developed world; TB, AIDS, hemorrhage (Waterhouse-Friderichsen in meningococcemia), metastases elsewhere. Symptoms — fatigue, weight loss, hyperpigmentation (high ACTH cross-reacts with MSH receptor), salt craving, hypotension. Labs — low cortisol, high ACTH, hyponatremia, hyperkalemia. ACTH stim test confirms — cortisol fails to rise. Treat — hydrocortisone (15-25 mg/day in divided doses), fludrocortisone 0.05-0.2 mg/day, stress-dose for illness or surgery.
When are stress-dose steroids needed?
Patients on chronic steroids may not mount cortisol response to stress. Hydrocortisone 100 mg IV q8h for major surgery, sepsis, trauma; lower doses for minor illness. Patients on >5 mg prednisone for >3 weeks within past year — assume HPA suppression. Failure to give stress dose risks adrenal crisis — hypotension refractory to fluids and pressors, hypoglycemia, hyperkalemia, hyponatremia. Treat suspected crisis empirically with hydrocortisone 100 mg before workup.
What is pheochromocytoma?
Catecholamine-secreting tumor of adrenal medulla (or extra-adrenal paraganglioma). Classic triad — episodic headache, palpitations, sweating with hypertension. Many are sustained hypertensive. Genetic syndromes — MEN 2A/2B (RET), VHL, NF1, hereditary paraganglioma syndromes (SDH mutations). Diagnosis — plasma free metanephrines or 24-hr urine metanephrines; CT or MRI to localize; MIBG scan for metastatic. Treat — alpha blockade (phenoxybenzamine or doxazosin) for at least 7-14 days before beta blocker, then surgical resection.
How do catecholamines act?
Epinephrine — alpha (vasoconstriction, peripheral), beta-1 (heart rate, contractility), beta-2 (bronchodilation, vasodilation in muscle). Norepinephrine — predominantly alpha (vasoconstriction); some beta-1. Pharmacologic uses — epinephrine for anaphylaxis (0.3 mg IM) and cardiac arrest (1 mg IV); norepinephrine first-line vasopressor in septic shock; phenylephrine pure alpha; isoproterenol pure beta. Beta blockers — selective (metoprolol blocks beta-1), nonselective (propranolol blocks beta-1 and beta-2 — caution in asthma).
How does chronic stress affect health?
Sustained cortisol — visceral obesity, insulin resistance, hypertension, dyslipidemia (metabolic syndrome). Immune suppression — slower wound healing, increased infections. Hippocampal atrophy — memory and depression. Bone resorption — osteoporosis. Sleep disruption from elevated nighttime cortisol. Psychological — anxiety, depression. Treatment — stress reduction (mindfulness shows cortisol reduction in trials), exercise, sleep hygiene, social support, treat depression. Chronic glucocorticoid therapy mimics this picture.