Treatment of Adrenal Insufficiency
The primary treatment for adrenal insufficiency is lifelong glucocorticoid replacement with hydrocortisone 15-25 mg daily in divided doses (typically 2-3 times per day), plus fludrocortisone 50-200 μg once daily for patients with primary adrenal insufficiency. 1, 2, 3
Maintenance Glucocorticoid Replacement
Hydrocortisone is the preferred first-line glucocorticoid because it most closely mimics physiologic cortisol secretion. 1, 2, 4
Dosing: Start with 15-25 mg daily, divided into 2-3 doses to approximate the natural cortisol rhythm. 1, 2, 3
Typical schedule: 10 mg upon waking + 5 mg at midday + 2.5 mg in the afternoon (the Endocrine Society's recommended three-dose regimen). 1, 2
Timing is critical: The first dose must be taken immediately upon waking, and the last dose should be at least 6 hours before bedtime to prevent sleep disturbances. 1, 2
Alternative glucocorticoid: Cortisone acetate 18.75-31.25 mg daily in divided doses can be used if hydrocortisone is unavailable. 1
Avoid synthetic glucocorticoids (like dexamethasone or prednisone) as first-line therapy due to undesirable long-term metabolic effects, though they may be used when oral hydrocortisone is not feasible. 5, 6
Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)
Fludrocortisone is required for all patients with primary adrenal insufficiency to replace aldosterone deficiency. 1, 2, 7
Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during the third trimester of pregnancy. 1, 3
Salt intake: Patients should consume salt and salty foods without restriction. 1, 3
Secondary adrenal insufficiency does not require mineralocorticoid replacement because aldosterone production remains intact. 4
Management of Adrenal Crisis (Life-Threatening Emergency)
Adrenal crisis requires immediate treatment without waiting for diagnostic confirmation. 2, 3
Hydrocortisone: 100 mg IV bolus immediately, followed by 100 mg IV/IM every 6-8 hours (or 100-300 mg/day as continuous infusion). 1, 2, 3
Fluid resuscitation: Rapid IV administration of 0.9% normal saline at 1 L/hour initially, followed by 3-4 L over 24 hours with frequent hemodynamic monitoring. 1, 2, 3
Taper: Once stabilized, taper parenteral glucocorticoids over 1-3 days back to oral maintenance therapy. 1, 2
Treat the precipitant: Identify and treat the underlying cause (infection, trauma, surgery, gastrointestinal illness). 3, 8
Stress Dosing Adjustments
During minor illness with fever: Double or triple the usual oral glucocorticoid dose. 1, 3, 4
Major surgery: 100 mg hydrocortisone IM before anesthesia, then 100 mg IM every 6 hours until able to resume oral medications. 1, 3
Minor surgery: 100 mg hydrocortisone IM before anesthesia, then double the oral dose for 24 hours. 1
During delivery: 100 mg hydrocortisone IV bolus, repeated every 6 hours as needed. 2, 3
Prevention of Adrenal Crisis
All patients must receive comprehensive education and emergency supplies. 2, 8
Medical alert identification: Every patient should wear a medical alert bracelet or necklace. 1, 2, 3
Emergency injectable hydrocortisone: Prescribe 100 mg IM hydrocortisone with training for self-administration or family member administration. 4, 8
Steroid emergency card: Provide written documentation of the diagnosis and emergency treatment requirements. 3, 8
Common precipitants to recognize: Gastrointestinal illness with vomiting/diarrhea, infections, surgical procedures, injuries, and severe allergic reactions. 1, 2
Follow-Up and Monitoring
Annual assessment is mandatory to detect under-replacement, over-replacement, and associated conditions. 1, 2
Clinical evaluation: Assess symptoms, weight, blood pressure (including orthostatic measurements). 1, 2
Laboratory tests: Serum sodium, potassium, glucose, HbA1c, and complete blood count. 1, 2
Screen for autoimmune conditions: Check TSH, free T4, and TPO antibodies annually (particularly in primary adrenal insufficiency). 1, 2, 3
Vitamin B12 levels: Screen for autoimmune gastritis. 1
Bone density: Assess every 3-5 years to monitor for glucocorticoid-related bone loss. 3
Common Pitfalls and How to Avoid Them
Under-replacement with mineralocorticoids is common and predisposes patients to recurrent adrenal crises—ensure adequate fludrocortisone dosing and liberal salt intake. 1
Drug interactions affecting glucocorticoid metabolism: 1
- Anti-epileptic drugs and barbiturates increase hydrocortisone requirements
- Antifungal drugs may affect metabolism
- Grapefruit juice and licorice decrease hydrocortisone requirements
If hypertension develops: Treat with vasodilators rather than stopping mineralocorticoid replacement (which remains essential). 1, 3
Signs of inadequate replacement: Weight loss, fatigue, postural hypotension, salt craving, hyperpigmentation (in primary adrenal insufficiency). 1, 8
Signs of excessive replacement: Weight gain, hypertension, edema. 1