What is the treatment for adrenal insufficiency?

Treatment for Adrenal Insufficiency

The cornerstone of adrenal insufficiency treatment is lifelong glucocorticoid replacement with hydrocortisone 15-25 mg daily in divided doses, plus fludrocortisone 50-200 μg daily for primary adrenal insufficiency. 1, 2

Maintenance Glucocorticoid Replacement

Hydrocortisone is the preferred glucocorticoid because it most closely mimics physiologic cortisol secretion. 1, 2, 3

Dosing Strategy:

• Total daily dose: 15-25 mg divided into 2-3 doses 1, 2
• Optimal three-dose schedule: 10 mg upon waking + 5 mg at midday + 2.5 mg in early afternoon 1, 2
• Critical timing: First dose immediately upon waking; last dose at least 6 hours before bedtime to avoid sleep disturbances 1, 2
• Alternative agent: Cortisone acetate 18.75-31.25 mg daily in divided doses if hydrocortisone unavailable 1

Important Drug Interactions Requiring Dose Adjustments:

• Anti-epileptic drugs and barbiturates increase hydrocortisone requirements 1
• Grapefruit juice and licorice decrease hydrocortisone requirements 4, 1
• Antifungal drugs may affect metabolism 1

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Fludrocortisone 50-200 μg once daily upon awakening is required for all patients with primary adrenal insufficiency. 1, 2, 5

Dosing Considerations:

• Higher doses up to 500 μg daily may be needed in children, younger adults, or during the third trimester of pregnancy 4, 1
• Patients should consume salt and salty foods without restriction 4, 1
• Avoid potassium-containing salts 4

Critical Drug Interactions to Avoid:

• Diuretics, acetazolamide, NSAIDs, carbenoxolone, and licorice should be avoided 4
• Drospirenone-containing contraceptives may require increased fludrocortisone 4

Common Pitfall:

Under-replacement with mineralocorticoids is extremely common and predisposes patients to recurrent adrenal crises. This is often compensated for by over-replacement of glucocorticoids, which creates additional problems. 4, 1

Management During Acute Illness and Stress

Minor Illness with Fever:

Double or triple the usual glucocorticoid dose during any febrile illness. 1, 6, 2

Major Surgery:

• Hydrocortisone 100 mg IM before anesthesia 1, 6, 2
• Continue 100 mg IM every 6 hours until able to take oral medications 1, 6, 2

Minor Surgery:

• Hydrocortisone 100 mg IM before anesthesia 1
• Then double oral dose for 24 hours 1

Adrenal Crisis (Life-Threatening Emergency):

Adrenal crisis requires immediate treatment without waiting for laboratory confirmation. 1, 6, 2

Immediate Management:

1. Hydrocortisone 100 mg IV bolus immediately 4, 1, 6, 2
   • If diagnosis uncertain and stimulation testing needed, use dexamethasone 4 mg instead (does not interfere with testing) 4
2. Rapid IV isotonic saline (0.9%) at 1 L/hour initially 1, 6, 2
3. Continue with 3-4 L over 24 hours with frequent hemodynamic monitoring 1, 6, 2
4. Hydrocortisone 100-300 mg/day as continuous infusion or divided IV/IM doses every 6 hours 1, 2

Tapering After Crisis:

Taper parenteral glucocorticoids over 1-3 days to oral maintenance therapy as the patient's condition improves. 1, 2

• For Grade 3-4 severity: Taper over 7-14 days after discharge 4
• For Grade 2 severity: Taper over 5-10 days 4

Special Populations

Pregnancy:

• Increase hydrocortisone by 2.5-10 mg daily during third trimester 4
• Fludrocortisone dose often needs to be increased during late pregnancy due to progesterone's anti-mineralocorticoid effects 4
• During delivery: Hydrocortisone 100 mg IV bolus, repeated every 6 hours if necessary 4, 2
• Double oral dose for 24-48 hours postpartum 4

Physical Activity:

Regular, accustomed physical activity does not require dose adjustment. 4, 2 For intense, prolonged, or unaccustomed exercise: Increase hydrocortisone and salt intake. 4, 2

Prevention of Adrenal Crisis

Mandatory Patient Education:

• All patients must wear medical alert identification jewelry 1, 6, 2
• Carry emergency injectable hydrocortisone 100 mg IM and know how to self-administer 6
• Increase glucocorticoid doses during intercurrent illnesses, vomiting, injuries, or other stressors 1, 6, 2

Common Precipitating Factors:

• Gastrointestinal illness with vomiting/diarrhea 1, 2
• Infections 1, 2
• Surgical procedures 1, 2
• Injuries 1, 2
• Severe allergic reactions 1, 2

Monitoring and Follow-Up

Annual Assessment Should Include:

• Symptoms, weight, and blood pressure (supine and standing) 1, 2
• Serum sodium, potassium, glucose, HbA1c, and complete blood count 1, 2
• Thyroid function tests (TSH, FT4, TPO antibodies) to screen for associated autoimmune conditions 1, 6, 2
• Vitamin B12 levels to screen for autoimmune gastritis 1, 6

Signs of Inadequate Replacement:

• Weight loss, fatigue, postural hypotension, salt craving, hyperpigmentation (in primary adrenal insufficiency) 1

Signs of Excessive Replacement:

• Weight gain, hypertension, edema 1

Critical Management Pitfall for Hypopituitarism

Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies, as this can trigger adrenal crisis. 4, 6 Always start corticosteroids several days before thyroid hormone. 4

Hypertension Management in Adrenal Insufficiency

Essential hypertension should be treated by adding a vasodilator, not by stopping mineralocorticoid replacement, although a dose reduction should be considered. 4, 1