Adrenocorticosteroids

Steroid Spectrum - Cortico-Classics

Adrenocorticosteroids: steroid hormones from cholesterol in adrenal cortex. Three classes:

• Glucocorticoids (e.g., Cortisol/Hydrocortisone)
  • Source: Zona Fasciculata.
  • Effects: Potent anti-inflammatory, immunosuppressive; metabolic (↑glucose, lipolysis, protein breakdown).
  • Regulation: HPA axis (CRH→ACTH→Cortisol); diurnal rhythm; negative feedback.
• Mineralocorticoids (e.g., Aldosterone)
  • Source: Zona Glomerulosa.
  • Effects: ECF volume & K⁺ balance; act on kidney tubules (↑Na⁺ reabsorption, ↑K⁺/H⁺ excretion).
  • Regulation: RAAS (Angiotensin II); plasma K⁺; ACTH (minor).
• Adrenal Androgens (e.g., DHEA, Androstenedione)
  • Source: Zona Reticularis.
  • Effects: Peripheral conversion to sex steroids; pubarche, female libido.

⭐ Cortisol exhibits pronounced diurnal secretion: peak early morning (~8 AM), nadir midnight.

Glucocorticoids - Power Potions

• Mechanism: Bind cytosolic receptors → translocate to nucleus → alter gene transcription (GREs).
• Metabolic Effects:
  • CHO: ↑Gluconeogenesis, ↓glucose use → Hyperglycemia.
  • Protein: ↑Catabolism → muscle wasting, osteoporosis.
  • Fat: Lipolysis & redistribution (moon face, buffalo hump).
• Anti-inflammatory/Immunosuppressive:
  • ↓PLA2 (↑Lipocortin-1), ↓COX-2, ↓Cytokines (ILs, TNF-α).
  • ↓Cellular immunity (T-cells), ↓Neutrophil & macrophage function.
• Other Key Effects:
  • CNS: Mood changes, psychosis.
  • GIT: ↑Acid → ulcer risk.
  • Bone: Osteoporosis (prolonged use).
  • Lung: ↑Fetal surfactant.
• Key Potencies (Anti-inflammatory): Hydrocortisone (1), Prednisolone (4), Dexamethasone (30).
  • Dexa/Beta: negligible mineralocorticoid effect. 📌 Mnemonic (Potency Order): Cute Hot Pharmacists & Physicians Marry Tall Beautiful Dames (C, H, P, P, M, T, B, D).

⭐ Dexamethasone suppression test is used to diagnose Cushing's syndrome and differentiate its causes.

Glucocorticoids: Uses & Cautions - Miracle Meds, Handle With Care

Uses (Miracle Meds):

• Anti-inflammatory/Immunosuppressive: Asthma, RA, SLE, IBD, organ transplant, severe allergies.
• Replacement: Addison's disease, CAH.
• Oncology: Lymphomas, ↓cerebral edema.
• Antenatal: Fetal lung maturation (<34 wks gestation).
• Diagnostic: Dexamethasone suppression test.

Key Adverse Effects (Handle With Care):

• Metabolic: Hyperglycemia, weight gain (Cushingoid: moon facies, buffalo hump).
• Musculoskeletal: Osteoporosis, myopathy, avascular necrosis.
• HPA Axis Suppression: ⚠️ Requires slow tapering after >2-3 weeks use.
• Immune: ↑Infection risk (e.g., TB reactivation), impaired wound healing.
• CNS/Eye: Psychosis, insomnia, mood changes; cataracts, glaucoma.
• GI: Peptic ulcers (↑risk with NSAIDs).
• Other: Hypertension, hypokalemia, growth retardation (children).

⭐ Sudden cessation of chronic glucocorticoids (therapy >2-3 weeks) can precipitate a life-threatening acute adrenal crisis. Always taper dose gradually.

Management Pearls:

• Use lowest effective dose, shortest possible duration.
• Monitor: BP, blood glucose, K+, Bone Mineral Density (BMD), eyes.
• Prophylaxis: Calcium/Vit D; PPI with high GI risk factors.

Mineralocorticoids & Modulators - Salt Savers & Spoilers

• Mineralocorticoids (Salt Savers):
  • Aldosterone: Endogenous. Acts on DCT/CD: ↑Na⁺/H₂O reabsorption, ↑K⁺/H⁺ excretion. Regulated by RAAS, K⁺.
  • Fludrocortisone: Synthetic. Potent mineralocorticoid, some glucocorticoid activity. Uses: Addison's disease (with hydrocortisone), salt-losing congenital adrenal hyperplasia (CAH).
• Mineralocorticoid Receptor Antagonists (MRAs - Salt Spoilers):
  • Spironolactone: K⁺-sparing diuretic. Uses: Primary hyperaldosteronism (Conn's), resistant hypertension, CHF, ascites. AEs: Hyperkalemia, gynecomastia, antiandrogenic effects.
  • Eplerenone: Selective MRA. Fewer AEs (e.g., gynecomastia) compared to spironolactone.
• Synthesis Inhibitor:
  • Metyrapone: Inhibits 11β-hydroxylase → ↓cortisol & ↓aldosterone synthesis. Uses: Cushing's syndrome (diagnosis & treatment).

⭐ Spironolactone, a K⁺-sparing diuretic for hyperaldosteronism, commonly causes gynecomastia due to its antiandrogenic effects on other steroid receptors.

High‑Yield Points - ⚡ Biggest Takeaways

• Glucocorticoids (e.g., Prednisolone) are powerful anti-inflammatory and immunosuppressive agents.
• Mineralocorticoids (e.g., Fludrocortisone) primarily manage sodium and water retention.
• Addison's disease requires lifelong replacement with both glucocorticoids and mineralocorticoids.
• Cushing's syndrome is caused by prolonged exposure to excess corticosteroids.
• Sudden withdrawal of chronic steroids can trigger a life-threatening adrenal crisis.
• Major side effects include osteoporosis, hyperglycemia, increased infection risk, and mood changes.
• Betamethasone and Dexamethasone are crucial for fetal lung maturation in premature births.