What is the treatment for adrenal insufficiency?

Treatment of Adrenal Insufficiency

The standard treatment for adrenal insufficiency consists of glucocorticoid replacement with hydrocortisone 15-25 mg daily in divided doses, plus mineralocorticoid replacement with fludrocortisone 50-200 μg daily for primary adrenal insufficiency. 1

Glucocorticoid Replacement

Dosing Regimens

• Hydrocortisone is the preferred glucocorticoid replacement, typically given in a total daily dose of 15-25 mg divided into 2-3 doses 1
• Common hydrocortisone dosing schedules include:
  • Three-dose regimen: 10 mg on waking, 5 mg at noon, 2.5-5 mg in late afternoon (not later than 6 hours before bedtime) 1
  • Two-dose regimen: 15 mg on waking, 5 mg in early afternoon; or 10 mg on waking, 10 mg in early afternoon 1
• Cortisone acetate can be used as an alternative at doses of 25-37.5 mg daily, also in divided doses 1
• Prednisolone (4-5 mg daily) should only be considered in cases of compliance problems, marked energy fluctuations, or when hydrocortisone is not tolerated 1

Dosing Considerations

• The first dose should be taken immediately upon waking 1
• For patients with morning nausea or lack of appetite, taking the first dose earlier and then going back to sleep may help relieve symptoms 1
• Night shift workers should adjust their dosing schedule according to their work pattern (e.g., 10 mg upon awakening before going to work) 1
• Dexamethasone should be avoided for chronic replacement 1

Mineralocorticoid Replacement

• Fludrocortisone is indicated for all patients with primary adrenal insufficiency at a dose of 50-200 μg (0.05-0.2 mg) once daily, usually taken upon awakening 1, 2
• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during the last trimester of pregnancy 1
• Dose adequacy is assessed by monitoring:
  • Blood pressure (both supine and standing)
  • Presence of salt cravings or lightheadedness
  • Peripheral edema
  • Serum electrolytes 1

Adrenal Crisis Management

• Adrenal crisis requires immediate treatment with:
  • Intravenous or intramuscular hydrocortisone 100 mg, followed by 100 mg every 6-8 hours until recovery 1
  • Isotonic (0.9%) sodium chloride solution at an initial rate of 1 L/hour until hemodynamic improvement 1
  • Identification and treatment of the underlying precipitant (e.g., infection) 1

Special Situations

Stress Dosing

• During minor illness (fever, infection):
  • Double or triple the usual oral glucocorticoid dose 3
• For surgery or major medical procedures:
  • Intravenous or intramuscular hydrocortisone and increased oral doses are required 1

Medication Interactions

• Drugs that may increase hydrocortisone requirements:
  • Anti-epileptics/barbiturates
  • Antituberculosis medications
  • Etomidate
  • Topiramate 1
• Drugs that may decrease hydrocortisone requirements:
  • Grapefruit juice
  • Licorice 1
• Medications to avoid with fludrocortisone:
  • Diuretics
  • Acetazolamide
  • Carbenoxolone
  • NSAIDs 1

Patient Education and Monitoring

• All patients should:
  • Wear medical alert identification jewelry
  • Carry a steroid alert card
  • Receive education on managing daily medications and minor illnesses
  • Have supplies for self-injection of parenteral hydrocortisone 1
• Annual follow-up should include:
  • Assessment of health and well-being
  • Measurement of weight and blood pressure
  • Serum electrolyte monitoring
  • Screening for development of other autoimmune disorders, particularly hypothyroidism 1
• Bone mineral density should be monitored every 3-5 years to assess for complications of glucocorticoid therapy 1

Common Pitfalls and Caveats

• Under-replacement with mineralocorticoids is common and sometimes compensated for by over-replacement with glucocorticoids 1
• Essential hypertension in a patient with primary adrenal insufficiency should be treated by adding a vasodilator and reducing (not stopping) the fludrocortisone dose 1
• Patients should be advised to eat sodium salt and salty foods without restriction and to avoid potassium-containing salts 1
• Despite adequate replacement therapy, patients with adrenal insufficiency may still experience impaired well-being and increased morbidity 4
• Adrenal crisis remains a life-threatening emergency that can occur even in patients on established replacement therapy, most commonly triggered by infectious diseases 5