How corticosteroids are tested on Step 1
Expect questions on the receptor mechanism, white-cell changes, choosing a steroid with no mineralocorticoid effect, or an adrenal crisis after abrupt withdrawal.
Steroids block phospholipase A₂ (via annexin A1), so they reduce both prostaglandins and leukotrienes. NSAIDs act one step later, at COX, and reduce only prostaglandins.
Mechanism
Corticosteroids are lipophilic and diffuse into cells, where they bind a receptor held in the cytoplasm by heat-shock proteins.
| Target | Effect |
|---|---|
| T cells | ↓ IL-2 → ↓ T-cell proliferation; lymphocytes redistribute and undergo apoptosis |
| Neutrophils | ↑ Count (demargination from vessel walls) but ↓ migration |
| Eosinophils, basophils | ↓ (useful in asthma and allergy) |
| Macrophages | ↓ IL-1, TNF-α, antigen presentation |
| Endothelium | ↓ Adhesion molecules, ↓ capillary permeability |
| Metabolism | ↑ Gluconeogenesis, protein catabolism, lipolysis; fat redistribution |
Steroid-induced neutrophilia with lymphopenia can mimic infection on a blood count.
Relative potency
Choose a steroid by anti-inflammatory potency, mineralocorticoid activity, and duration.
| Situation | Preferred steroid | Reason |
|---|---|---|
| Adrenal insufficiency, adrenal crisis | Hydrocortisone (± fludrocortisone) | Replaces both glucocorticoid and mineralocorticoid action |
| Cerebral edema from tumor | Dexamethasone | High potency, no sodium retention |
| Fetal lung maturity (preterm labor) | Betamethasone or dexamethasone | Cross the placenta |
| Dexamethasone suppression test | Dexamethasone | Not detected by cortisol assays |
| Asthma exacerbation, autoimmune flares | Prednisone or methylprednisolone | Intermediate duration, oral or IV |
| Asthma and COPD maintenance | Inhaled budesonide or fluticasone | Local effect; thrush risk |
Prednisone is a prodrug activated by the liver to prednisolone.
Adverse effects
Long-term systemic steroids reproduce Cushing syndrome.
Adrenal suppression and withdrawal
Exogenous glucocorticoids suppress CRH and ACTH; after weeks, the adrenal cortex atrophies.
| Issue | Management |
|---|---|
| More than 3 weeks of supraphysiologic doses | Taper slowly to allow HPA recovery |
| Surgery or acute illness while on chronic steroids | Stress-dose hydrocortisone |
| Abrupt withdrawal | Adrenal crisis: hypotension, shock, hypoglycemia, hyponatremia |
| Steroid-induced hyperglycemia | Mostly afternoon and evening; may need insulin |
Mineralocorticoid secretion (aldosterone) is preserved in secondary adrenal insufficiency because it depends on renin-angiotensin, not ACTH — so hyperkalemia is unusual.
A woman who has taken prednisone 20 mg daily for 2 years for rheumatoid arthritis has elective surgery. Her steroid is omitted. On the evening after surgery she is hypotensive and unresponsive to fluids, with glucose 52 mg/dL and sodium 129 mEq/L. What happened?
- Two years of prednisone suppressed ACTH, so her adrenals cannot raise cortisol for surgical stress.
- Without cortisol, vascular tone and response to catecholamines fall, causing refractory hypotension.
- Cortisol deficiency also causes hypoglycemia and hyponatremia (ADH release).
Answer. Acute adrenal crisis from HPA-axis suppression. Give IV hydrocortisone immediately with fluids and glucose; stress-dose coverage should have been given perioperatively.
