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) and mineralocorticoid replacement with 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 2-3 doses per day 1, 2
• Common dosing schedules include:
  • Three daily doses: 10 mg in the morning, 5 mg at midday, and 2.5 mg in the afternoon 1, 2
  • Two daily doses: 2/3 of the dose in the morning and 1/3 in the early afternoon 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, 2
• Cortisone acetate can be used as an alternative at 18.75-31.25 mg daily in divided doses 1

Mineralocorticoid Replacement

• Fludrocortisone (50-200 μg once daily) is required for patients with primary adrenal insufficiency 1, 4
• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during pregnancy 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 without delay for diagnostic procedures 5:
  • Hydrocortisone 100 mg IV bolus followed by 100-300 mg/day as continuous infusion or divided IV/IM doses every 6 hours 3, 1, 5
  • 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, 5
• Parenteral glucocorticoids should be tapered over 1-3 days to oral maintenance therapy as the patient's condition improves 1, 5

Stress Dosing for Illness and Procedures

• During minor illnesses with fever, the usual glucocorticoid dose should be doubled or tripled 1, 2
• For surgical 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

Prevention of Adrenal Crisis

• All patients should wear medical alert identification jewelry 1, 5
• Patient education should emphasize the importance of increasing steroid doses during intercurrent illnesses, vomiting, injuries, or other stressors 3, 1, 5
• Common precipitating factors for adrenal crisis include:
  • Gastrointestinal illness with vomiting/diarrhea 1, 5
  • Infections 1, 5
  • Surgical procedures without adequate steroid coverage 1, 5
  • Injuries or trauma 1, 5
  • Severe allergic reactions 1, 5

Follow-up and Monitoring

• Annual follow-up should include 3, 1, 2:
  • Assessment of symptoms, weight, and blood pressure
  • Laboratory tests: serum sodium, potassium, glucose, HbA1c, and complete blood count
• Screening for associated autoimmune conditions, particularly thyroid dysfunction (TSH, FT4, TPO-Ab) 3, 1, 2
• Evaluation of vitamin B12 levels to screen for autoimmune gastritis 1
• Signs of inadequate replacement include 3, 1:
  • Weight loss
  • Fatigue
  • Postural hypotension
  • Salt craving
  • Hyperpigmentation (in primary adrenal insufficiency)
• Signs of excessive replacement include weight gain, hypertension, and edema 1

Common Pitfalls and Caveats

• Under-replacement with mineralocorticoids is common and can predispose patients to recurrent adrenal crises 1, 3
• Medications that can affect glucocorticoid metabolism (requiring dose adjustments) include 1:
  • Anti-epileptic drugs and barbiturates (may increase hydrocortisone requirements)
  • Antifungal drugs (may affect metabolism)
  • Grapefruit juice and licorice (may decrease hydrocortisone requirements)
• Essential hypertension in patients with adrenal insufficiency should be treated with vasodilators rather than by stopping mineralocorticoid replacement 1
• Despite optimized replacement therapy, patients with adrenal insufficiency often experience reduced quality of life and increased mortality compared to the general population 6, 7