What is the difference between hydrocortisone and dexamethasone in the treatment of adrenal insufficiency?

Hydrocortisone vs Dexamethasone in Adrenal Insufficiency

Hydrocortisone is the preferred treatment for adrenal insufficiency, while dexamethasone should only be used in specific emergency situations when diagnosis is uncertain or when hydrocortisone is unavailable. 1

Key Differences

Pharmacological Properties

• Hydrocortisone (cortisol):

  • Structurally identical to endogenous cortisol 1
  • Has both glucocorticoid and mineralocorticoid activity 1
  • Short half-life (approximately 90 minutes) 1
  • Allows for recreation of the natural diurnal rhythm 1
  • Considered physiological replacement therapy 2

• Dexamethasone:

  • Synthetic glucocorticoid with no mineralocorticoid activity 1, 3
  • Much more potent (0.1mg dexamethasone ≈ 10mg hydrocortisone) 1
  • Longer duration of action 3
  • Cannot replicate natural cortisol rhythm 1

Clinical Applications

Primary Adrenal Insufficiency

• Hydrocortisone is the drug of choice 1, 3

  • Typical dosing: 15-25mg daily in divided doses (e.g., 10mg morning, 5mg afternoon, 2.5mg evening) 1
  • Provides both glucocorticoid and necessary mineralocorticoid effects 1
  • Usually requires additional fludrocortisone (0.05-0.1mg/day) for mineralocorticoid replacement 1

• Dexamethasone is inadequate as sole therapy 1

  • Lacks mineralocorticoid activity required in primary adrenal insufficiency 1
  • May be used in emergencies when diagnosis is uncertain and ACTH stimulation testing is needed 1

Secondary Adrenal Insufficiency (Central)

• Hydrocortisone remains first choice 1

  • Dosing similar to primary insufficiency but without fludrocortisone 1
  • Better mimics physiological cortisol patterns 4, 5

• Dexamethasone can be considered in specific situations 1

  • When hydrocortisone is unavailable 1
  • In major surgery when used as antiemetic (8mg dexamethasone ≈ 200mg hydrocortisone equivalent) 1

Dosing Recommendations

Maintenance Therapy

• Hydrocortisone:

  • Standard regimen: 15-25mg daily in 2-3 divided doses 1
  • Most physiological regimen: 10mg morning, 5mg midday, 5mg afternoon 6
  • Weight-adjusted dosing reduces interpatient variability 7

• Dexamethasone:

  • Not recommended for routine maintenance therapy 1, 3

Stress Dosing for Surgery/Illness

• Hydrocortisone:

  • Major surgery: 100mg IV at induction, followed by 200mg/24h continuous infusion 1
  • Moderate stress: 2-3 times maintenance dose 1
  • Continuous IV infusion provides more stable cortisol levels than intermittent boluses 8

• Dexamethasone:

  • Emergency use: 4mg IV if diagnosis uncertain and stimulation testing needed 1
  • Major surgery: 6-8mg IV may suffice for 24h in secondary adrenal insufficiency 1

Common Pitfalls and Caveats

• Mineralocorticoid deficiency: Dexamethasone provides no mineralocorticoid activity, potentially leading to life-threatening hyponatremia and hypotension in primary adrenal insufficiency 1

• Diagnostic interference: Dexamethasone interferes with cortisol assays and ACTH stimulation tests, while hydrocortisone does not 1

• Over-replacement risks: Long-term dexamethasone use can lead to more pronounced metabolic side effects due to its potency and longer half-life 3, 4

• Stress dosing education: All patients need education on stress dosing and should wear a medical alert bracelet 1

• Timing considerations: Hydrocortisone should be given in a pattern that mimics natural cortisol rhythm (higher in morning, lower in evening) 1, 5