What is the primary treatment for adrenal insufficiency?

Treatment of Adrenal Insufficiency

The primary treatment for adrenal insufficiency consists of glucocorticoid replacement (hydrocortisone 15-25 mg daily in divided doses) and mineralocorticoid replacement (fludrocortisone 50-200 μg daily) for patients with primary adrenal insufficiency. 1, 2

Maintenance Therapy

Glucocorticoid Replacement

• Hydrocortisone is the preferred glucocorticoid for replacement therapy, typically administered in a total daily dose of 15-25 mg divided into multiple doses (usually 2-3 times daily) 1, 2
• Common dosing schedules include:
  • Three doses: 10 mg + 5 mg + 2.5 mg (morning, midday, afternoon)
  • Two doses: 15 mg + 5 mg or 10 mg + 10 mg (morning, midday) 1
• Cortisone acetate can be used as an alternative at 18.75-31.25 mg daily in divided doses 1
• Prednisolone (3-5 mg daily) may be considered in cases of compliance problems or when hydrocortisone is not tolerated 1, 3
• The first dose should be taken immediately upon waking, and the last dose should be taken at least 6 hours before bedtime to avoid sleep disturbances 1

Mineralocorticoid Replacement

• Fludrocortisone (50-200 μg once daily) is required for patients with primary adrenal insufficiency 4, 2
• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during the last trimester of pregnancy 1
• Mineralocorticoid replacement should be restarted when hydrocortisone dose falls below 50 mg/day during recovery from an adrenal crisis 1
• Patients should be advised to consume salt and salty foods without restriction 1

Management During Stress and Illness

Adrenal Crisis Management

• Adrenal crisis requires immediate treatment with:
  • Hydrocortisone 100 mg IV bolus followed by 100-300 mg/day as continuous infusion or divided IV/IM doses every 6 hours 1
  • Rapid IV administration of isotonic saline (0.9%) at an initial rate of 1 L/hour, followed by 3-4 L over 24 hours with frequent hemodynamic monitoring 1
  • Treatment of any precipitating conditions (infections, injuries, etc.) 1
• Parenteral glucocorticoids should be tapered over 1-3 days to oral maintenance therapy as the patient's condition improves 1

Dose Adjustments for Special Situations

• Surgery and invasive procedures:
  • Major surgery: 100 mg hydrocortisone IM before anesthesia, followed by 100 mg IM every 6 hours until able to take oral medications 1
  • Minor surgery: 100 mg hydrocortisone IM before anesthesia, then double oral dose for 24 hours 1
  • Dental procedures: Extra morning dose 1 hour prior to procedure 1
• Intercurrent illness:
  • Double or triple the usual glucocorticoid dose during minor illnesses with fever 1
  • Seek immediate medical attention if unable to retain oral medication due to vomiting 1

Prevention of Adrenal Crisis

• All patients should:
  • Wear medical alert identification jewelry 1
  • Carry a steroid emergency card 5
  • Have injectable hydrocortisone available for emergency use 5
  • Receive education on self-management during illness and stress 1
• Patient education should emphasize the importance of increasing steroid doses during intercurrent illnesses, vomiting, injuries, or other stressors 1
• Common precipitating factors for adrenal crisis include:
  • Gastrointestinal illness with vomiting/diarrhea
  • Infections
  • Surgical procedures
  • Injuries
  • Severe allergic reactions 1

Follow-up and Monitoring

• Annual follow-up should include:
  • Assessment of symptoms, weight, and blood pressure 1
  • Laboratory tests: serum sodium, potassium, glucose, HbA1c, and complete blood count 1
  • Screening for associated autoimmune conditions, particularly thyroid dysfunction (TSH, FT4, TPO-Ab) 1
  • Evaluation of vitamin B12 levels to screen for autoimmune gastritis 1
• Signs of inadequate replacement include:
  • Weight loss
  • Fatigue
  • Postural hypotension
  • Salt craving
  • Hyperpigmentation (in primary adrenal insufficiency) 1
• Signs of excessive replacement include weight gain, hypertension, and edema 1

Common Pitfalls and Caveats

• Delayed diagnosis is common due to non-specific symptoms; maintain high clinical suspicion to prevent life-threatening adrenal crisis 6, 5
• Under-replacement with mineralocorticoids is common and can predispose patients to recurrent adrenal crises 1
• Medications that can affect glucocorticoid metabolism (requiring dose adjustments) include:
  • Anti-epileptic drugs and barbiturates (may increase hydrocortisone requirements)
  • Antifungal drugs (may affect metabolism)
  • Grapefruit juice and licorice (may decrease hydrocortisone requirements) 1
• Medications that can interact with fludrocortisone include diuretics, NSAIDs, and certain contraceptives 1
• Essential hypertension in patients with adrenal insufficiency should be treated with vasodilators rather than by stopping mineralocorticoid replacement 1