How to treat adrenal insufficiency after sudden suspension of corticosteroids (cortisone)

Treatment of Adrenal Insufficiency After Sudden Corticosteroid Withdrawal

Immediately initiate hydrocortisone replacement therapy at physiologic doses (15-25 mg daily in divided doses) for patients who develop adrenal insufficiency after abrupt corticosteroid cessation, with stress-dose coverage (hydrocortisone 100 mg IV bolus followed by 50-100 mg every 6-8 hours) if the patient presents with adrenal crisis symptoms including hypotension, severe gastrointestinal symptoms, or cardiovascular collapse. 1, 2, 3

Immediate Assessment and Risk Stratification

When a patient presents after sudden corticosteroid discontinuation, first determine the severity of presentation:

• Adrenal crisis (life-threatening): Hypotension unresponsive to fluids, altered mental status, severe nausea/vomiting/diarrhea, cardiovascular collapse, or syncope 2, 4
• Moderate-severe symptoms: Significant fatigue, persistent gastrointestinal symptoms, orthostatic hypotension, or hyponatremia 1, 4
• Mild symptoms: Fatigue, mild nausea, anorexia without hemodynamic compromise 3, 5

The risk of clinically significant adrenal insufficiency is highest in patients who received prednisolone ≥5 mg daily (or equivalent) for ≥4 weeks, with approximately 50% developing biochemical adrenal insufficiency during or immediately after withdrawal 6, 5. Clinical indicators peak during the withdrawal period (1 month before and after cessation), with incidence rate ratios of 2.5 for hypotension, 1.7 for gastrointestinal symptoms, and 1.5 for hyponatremia compared to baseline 4.

Treatment Protocol by Severity

For Adrenal Crisis (Severe Presentation)

Do not delay treatment for diagnostic testing - this is a medical emergency with potential for fatal outcome 2, 7:

• Hydrocortisone 100 mg IV bolus immediately upon recognition 2, 3
• Rapid IV fluid resuscitation: 1 liter normal saline over first hour, followed by 2-3 additional liters at slower rate 2
• Continue hydrocortisone 50-100 mg IV every 6-8 hours for first 24-48 hours 2, 8
• Draw blood for cortisol, ACTH, electrolytes, and glucose before first dose if possible, but never delay treatment 2
• Monitor vital signs frequently, particularly blood pressure and heart rate 2

After 24-48 hours of clinical improvement, taper over 3-5 days to oral maintenance therapy 2:

• Transition to oral hydrocortisone 15-25 mg daily in divided doses (typically two-thirds in morning, one-third in early afternoon) 1, 3
• If tapering from high IV doses, double the oral maintenance dose for 48 hours before returning to standard replacement 6

For Moderate-Severe Symptoms (Non-Crisis)

• Start hydrocortisone 20-30 mg in morning and 10-20 mg in afternoon (total 30-50 mg daily initially) 1
• Administer first dose immediately after waking, last dose at least 6 hours before bedtime to mimic natural cortisol rhythm 1
• Taper to maintenance dose (15-25 mg daily total) over 5-10 days as symptoms improve 1, 3
• Monitor for clinical improvement of fatigue, nausea, abdominal pain, and blood pressure stabilization 1

For Mild Symptoms

• Begin physiologic replacement with hydrocortisone 15-25 mg daily in divided doses 1, 3
• Alternative: Prednisone 3-5 mg daily (though hydrocortisone is preferred due to better safety profile) 3
• Titrate based on symptom response, up to maximum 30 mg daily for outpatient management 1

Critical Management Principles

The hypothalamic-pituitary-adrenal axis suppression can persist for up to 12 months after glucocorticoid discontinuation, requiring stress-dose coverage during this entire period for any physiological stress 7, 5. This is a common pitfall - clinicians often underestimate the duration of vulnerability.

Stress Dosing Protocol (Essential for All Patients)

• Minor illness: Double usual oral dose for 24-48 hours, then taper back 1, 2
• Severe illness or surgery: 100 mg hydrocortisone IM/IV immediately, followed by 100 mg every 6-8 hours until recovered 1, 2
• Dental procedures: Extra morning dose 1 hour prior 1
• 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 1

Monitoring and Follow-up

• Schedule follow-up in 2-4 weeks to reassess symptoms and adjust medication 1
• Monitor weight, blood pressure (including orthostatic measurements), and serum electrolytes at least annually 1, 2
• Consider testing for HPA axis recovery after 3 months of maintenance therapy, especially in glucocorticoid-induced cases 1, 9
• Morning cortisol <5 µg/dL with high ACTH suggests primary adrenal insufficiency; cortisol 5-10 µg/dL with low/normal ACTH suggests secondary or glucocorticoid-induced insufficiency 3

Essential Patient Education and Safety Measures

All patients require comprehensive education on self-management - studies show high rates of poor confidence and delayed treatment in acute settings 5:

• Prescribe emergency injectable hydrocortisone kit (100 mg IM) with training on self-administration 1, 2, 3
• Medical alert bracelet for adrenal insufficiency is mandatory 1, 2
• Provide written instructions on stress dosing for sick days 1, 2
• Advise taking salt and salty foods ad libitum; avoid licorice and grapefruit juice 1
• Educate on warning signs requiring immediate medical attention: persistent vomiting, severe weakness, confusion, or inability to take oral medications 2, 3

Common Pitfalls to Avoid

• Never taper corticosteroids too quickly before clinical stabilization - this precipitates recurrent crisis 2, 7
• Do not use dexamethasone for treatment of adrenal insufficiency in this context (it is not recommended for critical illness-related corticosteroid insufficiency) 8
• Inadequate fluid resuscitation alongside corticosteroid administration is a frequent error in crisis management 2
• Failing to provide stress-dose education leads to preventable adrenal crises - over 70% of cases are identified during acute hospital admissions where diagnosis is easily missed 5
• If prednisone is used instead of hydrocortisone, use lower doses due to reports of reduced survival with higher doses 1

Special Consideration: Duration of Risk

The withdrawal period carries the highest risk, but clinical indicators including hypotension and gastrointestinal symptoms remain elevated for up to 7 months after cessation compared to baseline 4. Risk factors for more severe or prolonged insufficiency include concurrent antibiotic use, higher average daily glucocorticoid dose, higher cumulative dose, and older age 4. This underscores the need for prolonged vigilance and patient education extending well beyond the immediate withdrawal period.