The adrenal cortex makes glucocorticoids (cortisol), mineralocorticoids (aldosterone), and androgens. Release of cortisol is controlled by the hypothalamic-pituitary-adrenal (HPA) axis: CRH → ACTH → cortisol, which feeds back to suppress CRH and ACTH.

Glucocorticoids enter cells, bind cytoplasmic receptors, and change gene transcription:

• Anti-inflammatory: block phospholipase A2 and cyclooxygenase-2 production → fewer prostaglandins and leukotrienes; stabilize capillaries; reduce leukocyte migration
• Immunosuppressive: reduce lymphocytes, cytokines, and antibody production
• Metabolic: raise blood glucose (gluconeogenesis, insulin resistance), break down protein and bone, redistribute fat
• Mineralocorticoid effect (varies by drug): sodium and water retention, potassium loss

Exogenous glucocorticoids suppress the HPA axis. After weeks of use, the adrenal glands shrink and cannot respond to stress — the basis of tapering and stress dosing. Suppression is possible with doses equal to or above about prednisone 20 mg daily for 3 weeks or more, and should be assumed in clients with Cushingoid features; courses under 3 weeks rarely cause clinically important suppression.

Mineralocorticoids (fludrocortisone) act on kidney tubules to retain sodium and excrete potassium.

Indications: adrenal insufficiency (replacement), asthma and COPD exacerbations, allergic reactions and anaphylaxis (adjunct), rheumatoid arthritis, lupus, vasculitis, inflammatory bowel disease, dermatologic disease, cerebral edema from tumors (dexamethasone), transplant rejection, some cancers and leukemias, fetal lung maturity (betamethasone or dexamethasone in threatened preterm birth), multiple sclerosis relapse, myasthenia gravis, nausea with chemotherapy, and severe COVID-19 requiring oxygen (dexamethasone).

Equivalent doses and properties

Other routes — inhaled (fluticasone, budesonide, beclomethasone) for asthma and COPD; intranasal for allergic rhinitis; topical creams in potency classes; intra-articular injections; ophthalmic drops. Local routes greatly reduce systemic effects but do not eliminate them at high doses.

Effects depend on dose and duration. Short courses mainly cause the first group; long-term use causes the second.

Short-term (days to weeks)

• Hyperglycemia (especially afternoon and evening with morning dosing)
• Insomnia, mood changes, euphoria, irritability, steroid psychosis (dose-related)
• Increased appetite, fluid retention, hypertension, hypokalemia
• GI upset; peptic ulcer risk (mainly when combined with NSAIDs)
• Leukocytosis (neutrophil rise without infection)

Long-term (months)

• Cushingoid features: moon face, buffalo hump, truncal obesity, thin skin, striae, easy bruising, acne, hirsutism
• Osteoporosis and fractures; avascular necrosis of the hip
• Proximal muscle weakness (steroid myopathy)
• Infection — increased risk and masked signs (fever and inflammation blunted); reactivation of TB, hepatitis B, herpes zoster; opportunistic infections (Pneumocystis, fungal)
• Impaired wound healing
• Cataracts and glaucoma
• Growth suppression in children
• Adrenal suppression → adrenal crisis if stopped abruptly or during stress
• Diabetes, dyslipidemia, hypertension

Inhaled corticosteroids — oral candidiasis (thrush), hoarseness; slight growth slowing in children; pneumonia risk in COPD.

Topical — skin atrophy, striae, telangiectasia; systemic absorption with large areas, occlusion, or potent products in infants.

Fludrocortisone — hypertension, edema, hypokalemia, weight gain.

• Systemic fungal infections (contraindication) and hypersensitivity
• Live vaccines are contraindicated at immunosuppressive doses (commonly prednisone 20 mg/day or more for 14 days or more, or 2 mg/kg/day or more in children under 10 kg); wait at least 1 month after stopping before giving a live vaccine; inactivated vaccines may give a weaker response
• Caution: active or latent tuberculosis (screen before long-term high-dose use), hepatitis B (screen, reactivation), untreated infections, diabetes, hypertension, heart failure, peptic ulcer, osteoporosis, glaucoma, psychiatric illness, recent intestinal anastomosis, myasthenia gravis (initial high doses can worsen weakness)
• Children: monitor growth; older adults: fracture and delirium risk

Major interactions

• NSAIDs and aspirin — increased GI bleeding and ulcers
• Potassium-wasting diuretics (loop, thiazide), amphotericin B — hypokalemia; digoxin toxicity when potassium falls
• Antidiabetic drugs and insulin — higher doses needed
• CYP3A4 inducers (rifampin, phenytoin, carbamazepine) lower steroid effect; strong CYP3A4 inhibitors (ritonavir, ketoconazole) raise levels — Cushing syndrome and adrenal suppression reported even with inhaled fluticasone plus ritonavir
• Warfarin — altered INR; monitor
• Fluoroquinolones — increased tendon rupture risk
• Other immunosuppressants — additive infection risk

Pregnancy and lactation — used when clearly needed. Prednisone and prednisolone are largely inactivated by the placenta, so fetal exposure is low; dexamethasone and betamethasone cross the placenta — which is why they are used for fetal lung maturity. Prolonged maternal use can cause neonatal adrenal suppression (monitor the newborn). Compatible with breastfeeding at usual doses; with high doses, feeding may be delayed about 4 hours after the dose.

Listed in priority order.

1. Adrenal crisis — hypotension or shock, vomiting, abdominal pain, confusion, hypoglycemia, hyponatremia, hyperkalemia in a client on long-term steroids who stopped suddenly or is under stress. Establish IV access and give IV hydrocortisone 100 mg and IV 0.9% saline immediately per protocol — do not wait for test results.
2. Infection surveillance — signs are masked: check temperature, wounds, lungs, mouth (thrush), and urine; report subtle changes (malaise, localized pain, low-grade fever). Hand hygiene; avoid sick contacts.
3. Blood glucose — monitor at least daily, often before meals and at bedtime, especially in diabetes; a common hospital target is 100–180 mg/dL (5.6–10.0 mmol/L); correction insulin as ordered (NPH is often matched to morning prednisone).
4. Fluid and electrolytes — daily weight, BP, edema, potassium (normal 3.5–5.0 mEq/L [mmol/L]) and sodium; report weight gain above about 1 kg (2.2 lb) in a day or 2 kg (5 lb) in a week.
5. Never stop long-term therapy abruptly — ensure taper orders; do not omit doses when NPO — obtain an IV order. Stress dosing for surgery, trauma, or severe illness per protocol.
6. GI protection — give oral doses with food; report epigastric pain or black stools; a proton pump inhibitor may be ordered when combined with NSAIDs or anticoagulants.
7. Mental status — insomnia, mood swings, psychosis; safety precautions.
8. Musculoskeletal — fall prevention; bone density (DXA), calcium and vitamin D, and bone-protective drugs for long-term use (commonly when prednisone 2.5 mg/day or more is expected for 3 months or more).
9. Eyes and growth — periodic eye exams for long-term use; plot height in children.
10. Skin — gentle handling, pressure injury prevention, careful tape use.

• Take once-daily doses in the morning with food (mimics the natural cortisol rhythm and reduces insomnia and HPA suppression). Alternate-day regimens may be prescribed to limit suppression.
• Never stop suddenly or skip doses after more than a few weeks of use — the dose must be tapered. Report weakness, dizziness, nausea, or fainting during tapering.
• Stress dosing ("sick-day rules") for clients with adrenal insufficiency or long-term therapy: double or triple the dose during fever or significant illness as instructed; seek care or use an emergency hydrocortisone injection if vomiting or unable to keep pills down. Carry a steroid card or medical identification.
• Avoid people with infections; report fever, sore throat, cough, painful urination, or wounds that do not heal — infection signs may be mild.
• Tell providers about steroid use before surgery, dental work, or vaccination; avoid live vaccines while on high doses.
• Check glucose as instructed; report excessive thirst or urination.
• Eat a diet rich in protein, calcium, and potassium, and limit sodium and concentrated sweets; stay physically active with weight-bearing exercise; avoid smoking and excess alcohol.
• Weigh daily; report swelling, rapid weight gain, black stools, vision changes, or severe mood changes.
• Inhaled steroids: use regularly (not for quick relief); rinse mouth and spit after each use; use a spacer.
• Topical steroids: thin layer; avoid face, groin, and occlusion unless prescribed; limit duration.

• Acute overdose of a corticosteroid is rarely dangerous; treatment is supportive (glucose, BP, electrolytes, mental status). There is no antidote.
• The main harms are chronic toxicity (Cushing syndrome, infection, bone loss) and withdrawal:
  • Adrenal crisis — life-threatening; IV hydrocortisone and fluids at once
  • Steroid withdrawal syndrome — fatigue, joint and muscle pain, anorexia, mood change during tapering without true adrenal failure; slower taper
  • Flare of the underlying disease when tapered too quickly
• Steroid-induced hyperglycemia crisis (HHS) in clients with diabetes on high doses — fluids and insulin per protocol.
• Rapid IV high-dose methylprednisolone can cause dysrhythmias, hypotension, and hyperglycemia — infuse over the ordered time (commonly at least 30 minutes for pulse doses) with monitoring.

• Glucocorticoids: anti-inflammatory, immunosuppressive, raise glucose, break down bone and muscle
• Hydrocortisone = adrenal replacement and crisis; dexamethasone = cerebral edema, long-acting, no mineralocorticoid effect; fludrocortisone = aldosterone replacement
• Equivalents: hydrocortisone 20 mg = prednisone 5 mg = methylprednisolone 4 mg = dexamethasone 0.75 mg
• Never stop long-term steroids abruptly → adrenal crisis; taper
• Adrenal crisis: IV hydrocortisone 100 mg + IV saline immediately; hypotension, hypoglycemia, hyperkalemia
• Sick-day rules: double or triple the dose; injection kit if vomiting; medical ID
• Infection signs are masked; no live vaccines at high doses; screen for TB and hepatitis B
• Monitor glucose, potassium, BP, weight; hypokalemia with diuretics → digoxin toxicity
• Give in the morning with food; NSAIDs + steroids = GI bleeding
• Long term: osteoporosis, cataracts, glaucoma, myopathy, growth suppression
• Inhaled steroids: rinse mouth (thrush)