What is the primary treatment for adrenal insufficiency?

Primary Treatment for Adrenal Insufficiency

The primary treatment for adrenal insufficiency is glucocorticoid replacement with hydrocortisone 15-25 mg daily divided into 2-3 doses, plus mineralocorticoid replacement with fludrocortisone 50-200 μg daily for patients with primary adrenal insufficiency. 1, 2, 3

Maintenance Glucocorticoid Therapy

Hydrocortisone is the preferred glucocorticoid because it most closely mimics physiological cortisol and avoids the undesirable metabolic long-term effects of synthetic glucocorticoids. 1, 2, 4

Dosing Schedule

• Total daily dose: 15-25 mg hydrocortisone divided into 2-3 doses (weight-adjusted dosing is preferable). 1, 2, 5
• Typical three-dose regimen: 10 mg upon waking + 5 mg at midday + 2.5 mg in afternoon. 1, 2
• First dose must be taken immediately upon waking, and the last dose should be taken 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 can be used if hydrocortisone is unavailable. 1

Critical Caveat

Dexamethasone and prednisone are less suitable as first-line treatment due to their longer half-lives and metabolic side effects, though prednisone 3-5 mg daily can be used in select cases. 6, 4, 5

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Fludrocortisone 50-200 μg once daily is required for all patients with primary adrenal insufficiency to replace aldosterone deficiency. 1, 2, 3

• Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during the last trimester of pregnancy. 1
• Patients should consume salt and salty foods without restriction to support mineralocorticoid function. 1
• Under-replacement with mineralocorticoids is a common pitfall that predisposes patients to recurrent adrenal crises. 1, 7
• Secondary adrenal insufficiency does not require mineralocorticoid replacement because the renin-angiotensin-aldosterone system remains intact. 4

Management During Acute Illness and Stress

Minor Illness with Fever

• Double or triple the usual glucocorticoid dose during minor illnesses with fever. 1, 2
• Even mild gastrointestinal upset can precipitate adrenal crisis because patients cannot absorb oral medication when they need it most. 7

Adrenal Crisis (Life-Threatening Emergency)

Treatment must never be delayed for diagnostic procedures. 7, 2

• Immediate hydrocortisone 100 mg IV bolus, followed by 100-300 mg/day as continuous infusion or divided IV/IM doses every 6 hours. 1, 7, 2
• Aggressive fluid resuscitation with 0.9% isotonic saline at 1 L/hour initially, followed by 3-4 L over 24 hours with frequent hemodynamic monitoring. 1, 7, 2
• Draw blood for cortisol, ACTH, and electrolytes before treatment, but do not delay therapy waiting for results. 7
• No separate mineralocorticoid is needed during acute crisis because high-dose hydrocortisone provides adequate mineralocorticoid activity. 7
• Taper parenteral glucocorticoids over 1-3 days to oral maintenance therapy as the patient's condition improves. 1, 2

Surgical Stress Dosing

• 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
• Delivery: 100 mg hydrocortisone IV bolus, repeated every 6 hours if necessary. 2

Prevention of Adrenal Crisis

All patients must wear medical alert identification jewelry and carry an emergency steroid card. 1, 2, 4

• Provide injectable hydrocortisone 100 mg IM with training for self-administration or family member administration during severe illness or vomiting. 7, 4, 8
• Patient education on "sick day rules" is essential: increase glucocorticoid doses during intercurrent illnesses, vomiting, injuries, or other stressors. 1, 7, 2, 8
• Common precipitating factors include: gastrointestinal illness with vomiting/diarrhea (most common), infections, surgical procedures, injuries, and severe allergic reactions. 1, 7, 2

Monitoring and Follow-Up

Annual Assessment

• Clinical evaluation: symptoms, weight, and blood pressure to detect signs of under- or over-replacement. 1, 2
• Laboratory tests: serum sodium, potassium, glucose, HbA1c, and complete blood count. 1, 2
• Screen for autoimmune conditions: TSH, FT4, TPO-Ab (thyroid dysfunction) and vitamin B12 (autoimmune gastritis). 1, 2

Signs of Inadequate Replacement

• Weight loss, fatigue, postural hypotension, salt craving, and hyperpigmentation (in primary adrenal insufficiency). 1, 8

Signs of Excessive Replacement

• Weight gain, hypertension, and edema. 1

Important Drug Interactions

Medications that accelerate cortisol clearance require dose adjustments: 1, 7

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

Critical Pitfall to Avoid

Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies, as this can trigger adrenal crisis. 7, 2