9.3 Corticosteroids
Corticosteroids include glucocorticoids (anti-inflammatory, immunosuppressive) and mineralocorticoids (salt/water balance). Understanding their mechanisms, uses, and significant adverse effects is essential for safe prescribing.
Glucocorticoids
Mechanism of Action
Bind intracellular glucocorticoid receptor → translocate to nucleus → modify gene transcription. Induce anti-inflammatory proteins (lipocortin/annexin-1), suppress pro-inflammatory cytokines (IL-1, IL-2, TNF-α, IFN-γ).
Common Glucocorticoids
- • Hydrocortisone (cortisol): Short-acting; physiologic replacement
- • Prednisone/Prednisolone: Intermediate-acting; most common
- • Methylprednisolone: IV formulation; less mineralocorticoid activity
- • Dexamethasone: Long-acting; potent; no mineralocorticoid activity
- • Betamethasone: Fetal lung maturation (crosses placenta)
Clinical Indications
- • Replacement: Adrenal insufficiency, CAH
- • Anti-inflammatory: Asthma, COPD, IBD, rheumatoid arthritis
- • Immunosuppression: Transplant, autoimmune diseases
- • Oncology: Lymphomas, leukemias, anti-emetic, cerebral edema
- • Allergic: Anaphylaxis, angioedema
⚠️ Major Adverse Effects (Chronic Use)
Metabolic:
- • Hyperglycemia, diabetes (↑ gluconeogenesis)
- • Dyslipidemia
- • Weight gain, central obesity
- • Cushingoid features
Musculoskeletal:
- • Osteoporosis, fractures (↓ osteoblasts)
- • Avascular necrosis (femoral head)
- • Myopathy (proximal muscle weakness)
- • Growth suppression (children)
Other:
- • Immunosuppression (↑ infections)
- • Cataracts, glaucoma
- • Peptic ulcers, GI bleeding
- • Psychiatric (mood changes, psychosis)
- • Skin thinning, striae, easy bruising
- • HPA axis suppression
Mineralocorticoids
Fludrocortisone
Mechanism:
Acts on mineralocorticoid receptors in distal tubule/collecting duct. Increases Na+ reabsorption, K+ and H+ secretion. Expands volume, increases BP.
Indications:
- • Primary adrenal insufficiency (Addison's disease)
- • Congenital adrenal hyperplasia (salt-wasting)
- • Orthostatic hypotension
Adverse Effects:
- • Hypertension, edema (volume expansion)
- • Hypokalemia, metabolic alkalosis
- • Heart failure exacerbation
- Monitor BP, K+, body weight
Adrenal Insufficiency
Primary (Addison's Disease)
Destruction of adrenal cortex (autoimmune, TB, hemorrhage). Deficiency of cortisol AND aldosterone.
Treatment:
- • Hydrocortisone: 15-25 mg/day (divided doses to mimic diurnal rhythm)
- • Fludrocortisone: 0.05-0.2 mg/day (mineralocorticoid replacement)
- • Increase dose during stress/illness
Secondary/Tertiary
Pituitary (↓ ACTH) or hypothalamic (↓ CRH) dysfunction. Cortisol deficiency but aldosterone preserved (regulated by renin-angiotensin).
Treatment:
- • Hydrocortisone or prednisone only
- • No fludrocortisone needed (RAAS intact)
Adrenal Crisis (Acute Adrenal Insufficiency)
Life-threatening: Hypotension, shock, hypoglycemia, hyperkalemia, hyponatremia. Triggered by stress (infection, surgery, trauma) in patient with unrecognized/undertreated adrenal insufficiency.
Emergency Treatment:
- 1. IV hydrocortisone: 100 mg bolus, then 50-100 mg q6-8h
- 2. IV saline: Aggressive volume resuscitation
- 3. Dextrose: If hypoglycemic
- 4. Identify and treat precipitant
Steroid Withdrawal & HPA Suppression
Tapering Considerations
Chronic glucocorticoid use (>2-3 weeks at supraphysiologic doses) suppresses HPA axis. Abrupt discontinuation can precipitate adrenal crisis.
When to Taper:
- • >3 weeks of prednisone ≥20 mg/day (or equivalent)
- • Any dose if patient has Cushingoid features
- • Evening doses more suppressive than morning
Tapering Strategy:
- • Gradual dose reduction (e.g., 5-10 mg/week)
- • Switch to physiologic doses (5-7.5 mg prednisone/day)
- • Consider ACTH stimulation test to assess recovery
- • May take months for full HPA recovery