What is the primary treatment for adrenal insufficiency?

Primary Treatment for Adrenal Insufficiency

The primary 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

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 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
  • Two daily doses: Higher dose in the morning (2/3 of total) and lower dose in the afternoon (1/3 of total) 3
• Cortisone acetate can be used as an alternative at 18.75-31.25 mg daily in divided doses 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
• A modified release hydrocortisone formulation (Plenadren) allowing once daily dosing has been introduced in Europe, but its role in therapy is still being evaluated 3

Mineralocorticoid Replacement

• Fludrocortisone (50-200 μg once daily) is required for patients with primary adrenal insufficiency 3, 4
• The tablets are usually taken in one dose upon awakening 3
• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during the last trimester of pregnancy 3
• Mineralocorticoid replacement is evaluated clinically by assessing:
  • Salt cravings
  • Lightheadedness
  • Blood pressure in supine and standing positions
  • Presence of peripheral edema 3
• Under-replacement is common and may predispose patients to recurrent adrenal crises 3

Management During Stress and Illness

• Adrenal crisis requires immediate treatment with:
  • Hydrocortisone 100 mg IV bolus followed by 100 mg IV/IM every 6-8 hours until recovered 3
  • Rapid IV administration of isotonic saline (0.9%) at an initial rate of 1 L/hour 3
• During minor illnesses with fever, the usual glucocorticoid dose should be doubled or tripled 1
• For surgery:
  • Major surgery: 100 mg hydrocortisone IM before anesthesia, followed by 100 mg IM every 6 hours 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 and carry a steroid alert card 3
• Patient education should emphasize the importance of increasing steroid doses during intercurrent illnesses, vomiting, injuries, or other stressors 2
• Common precipitating factors for adrenal crisis include:
  • Gastrointestinal illness with vomiting/diarrhea
  • Infections
  • Surgical procedures
  • Injuries
  • Severe allergic reactions 1

Medication Interactions and Considerations

• Medications that can affect glucocorticoid metabolism include:
  • Anti-epileptic drugs and barbiturates (may increase hydrocortisone requirements) 3
  • Antifungal drugs (may affect metabolism) 3
  • Grapefruit juice and licorice (may decrease hydrocortisone requirements) 3
• Medications that can affect fludrocortisone include:
  • Diuretics (avoid)
  • Acetazolamide (avoid)
  • NSAIDs (avoid)
  • Drospirenone-containing contraceptives (may need more fludrocortisone) 3

Follow-up and Monitoring

• Annual follow-up should include:
  • Assessment of symptoms, weight, and blood pressure
  • Laboratory tests: serum sodium, potassium, glucose, and complete blood count 1
• Screening for associated autoimmune conditions, particularly thyroid dysfunction 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

Special Considerations

• During pregnancy, hydrocortisone requirements may increase by 2.5-10 mg daily, particularly in the third trimester 3
• Fludrocortisone dose may need to be increased during late pregnancy due to the anti-mineralocorticoid effects of progesterone 3
• For intense or prolonged exercise, an increase in hydrocortisone and salt intake may be necessary 3
• Essential hypertension in patients with adrenal insufficiency should be treated with vasodilators rather than by stopping mineralocorticoid replacement 3