How to manage steroid-induced adrenal insufficiency?

Management of Steroid-Induced Adrenal Insufficiency

The cornerstone of managing steroid-induced adrenal insufficiency is physiologic hydrocortisone replacement at 15-25 mg daily in divided doses (morning and afternoon), combined with comprehensive patient education on stress dosing and emergency management. 1

Acute Management Based on Severity

Severe/Life-Threatening Adrenal Crisis

• Immediate treatment with IV hydrocortisone 100 mg bolus, followed by 100-300 mg/day as continuous infusion or 100 mg every 6-8 hours 2, 1
• Aggressive fluid resuscitation with 3-4 L isotonic saline at initial rate of 1 L/hour with frequent hemodynamic monitoring 2
• Hospitalize immediately; do not delay treatment for diagnostic testing 2
• Taper parenteral steroids over 1-3 days to oral maintenance once stabilized 2

Moderate Symptoms (Able to Perform Activities of Daily Living)

• Start hydrocortisone at 2-3 times maintenance dose (approximately 30-50 mg daily) 1
• Taper to physiologic maintenance (15-25 mg daily) over 5-10 days as symptoms improve 1
• Consider endocrine consultation for optimization 2

Mild Symptoms

• Begin physiologic replacement with hydrocortisone 15-25 mg daily in split doses 2, 1
• First dose immediately upon waking, last dose at least 6 hours before bedtime to mimic natural cortisol rhythm 2, 1
• Use the lowest dose compatible with health and sense of well-being 2, 1

Critical Patient Education Requirements

All patients must receive comprehensive education on the following, as failure to do so significantly increases mortality risk: 2, 1

• Stress dosing protocol: Double the usual oral dose for 24-48 hours during minor illness, then taper back 2, 1
• Emergency injectable hydrocortisone supplies with training on self-administration 2, 1
• Medical alert bracelet for adrenal insufficiency to trigger stress-dose corticosteroids by emergency medical services 2, 1
• Warning signs of adrenal crisis: severe weakness, confusion, abdominal pain, hypotension 3

Surgical and Procedural Management

The degree of steroid supplementation depends on procedure severity 2:

• Major surgery: 100 mg hydrocortisone IM just before anesthesia, continue 100 mg IM every 6 hours until able to eat/drink, then double oral dose for 48+ hours before tapering 2, 1
• Minor surgery/major dental: 100 mg hydrocortisone IM before procedure, double oral dose for 24 hours 2
• Dental procedures: Extra morning dose 1 hour prior 2, 1

Assessing Recovery of HPA Axis Function

A critical pitfall is attempting to test for adrenal insufficiency while patients are still on corticosteroids—this cannot be done accurately. 3

• Laboratory confirmation of adrenal insufficiency cannot be performed during active corticosteroid treatment 3
• Testing must be deferred until patient is ready to discontinue corticosteroid therapy 3
• Endocrinology consultation is essential for establishing a recovery and weaning protocol using hydrocortisone 3
• After tapering to physiologic doses, the HPA axis should be tested for recovery after 3 months of maintenance therapy 2, 3
• For checkpoint inhibitor-induced cases, assess every 3 months in the first year, then every 6 months with morning cortisol, ACTH, and/or low-dose cosyntropin stimulation test 3

Important Timing Considerations

When planning hormone replacement for multiple deficiencies, always start corticosteroids first—other hormones accelerate cortisol clearance and can precipitate adrenal crisis. 2

Monitoring and Follow-up

• Assess weight, blood pressure, and serum electrolytes at least annually 2, 1
• Monitor for clinical improvement of fatigue, nausea, abdominal pain, and hypotension 1
• Schedule follow-up in 2-4 weeks to reassess symptoms and adjust medication 1
• Monitor for development of iatrogenic Cushing's syndrome with excessive replacement 1

Common Pitfalls to Avoid

• ACTH stimulation testing can give false-negative results early in the course, as adrenal reserve declines slowly after pituitary stimulation is lost—in cases of clinical uncertainty, opt for replacement and test for ongoing need at 3 months 2
• Morning cortisol in patients on corticosteroids is not diagnostic, as measurement of therapeutic steroids in the assay varies 2
• Hydrocortisone must be held for 24 hours and other steroids for longer before endogenous function can be assessed 2
• If prednisone is used instead of hydrocortisone, consider lower doses (average daily dose over two months of 7.5 mg) due to reports of reduced survival on higher doses 2

Special Populations

• Children: Hydrocortisone dose should be 6-10 mg/m² of body surface area 2
• Pregnancy: May need increased hydrocortisone by 2.5-10 mg daily during third trimester; 100 mg hydrocortisone IM at onset of labor, double oral dose for 24-48 hours postpartum 2