My patient was tapered off prednisone too quickly; how should I manage the resulting adrenal insufficiency and disease flare?

Management of Too-Rapid Prednisone Taper

Immediately return to the pre-taper prednisone dose and maintain it for 4–8 weeks to re-establish disease control and allow HPA-axis stabilization, then resume tapering at a slower rate. 1

Immediate Actions

Restore Adequate Glucocorticoid Coverage

• Return to the last dose at which the patient was stable (the dose before symptoms began) and maintain this for 4–8 weeks until disease control is re-established. 1
• If the patient is acutely symptomatic with signs of adrenal crisis (severe fatigue, weakness, hypotension, nausea/vomiting, confusion), administer hydrocortisone 100 mg IV immediately without waiting for diagnostic testing. 2, 3
• For less severe symptoms, oral prednisone at the pre-taper dose is sufficient. 1

Distinguish Between Disease Flare and Adrenal Insufficiency

• Disease flare presents with return of the original inflammatory symptoms (arthritis, rash, fever, elevated inflammatory markers like ESR/CRP). 1
• Adrenal insufficiency presents with nonspecific symptoms: fatigue (50–95% of cases), nausea/vomiting (20–62%), anorexia, weight loss, orthostatic hypotension, hyponatremia, and hyperkalaemia. 4, 1
• Both conditions can coexist—a too-rapid taper can trigger both disease relapse and symptomatic adrenal insufficiency simultaneously. 1, 5

Diagnostic Evaluation (Once Stabilized)

Assess for Adrenal Insufficiency

• Do not perform cortisol testing while the patient is actively taking supraphysiologic prednisone doses—results will be falsely low due to iatrogenic HPA-axis suppression. 2
• Once the patient reaches a physiologic dose (≤5 mg prednisone daily), measure early-morning (8 AM) serum cortisol after withholding prednisone for 48 hours. 6, 2
• A morning cortisol <5 µg/dL indicates adrenal insufficiency**; values **>10 µg/dL (ideally >15–20 µg/dL) indicate adequate HPA-axis recovery. 6, 4
• If morning cortisol is intermediate (5–10 µg/dL), perform a cosyntropin stimulation test (0.25 mg IV/IM): a peak cortisol <500 nmol/L (18 µg/dL) at 60 minutes confirms adrenal insufficiency. 2, 4

Monitor Disease Activity

• Check disease-specific markers (ESR, CRP, ferritin, anti-dsDNA, complement levels, urinalysis) every 4–8 weeks during the first year of tapering to detect early relapse. 1

Corrected Tapering Protocol

General Principles

• Single daily morning dosing (before 9 AM) minimizes HPA-axis suppression and aligns with physiologic cortisol rhythms. 1, 3
• Tapering speed must be individualized based on the dose range: faster reductions are safe above 10 mg/day, but below 10 mg/day require 1 mg decrements every 4 weeks. 1

High-Dose Range (>30 mg/day → 10 mg/day)

• Reduce by 5 mg every week until reaching 10 mg/day (completed in 4–8 weeks depending on disease stability). 1

Medium-Dose Range (10–30 mg/day → 10 mg/day)

• Reduce by 5 mg every week until reaching 10 mg/day, then slow the taper. 1

Low-Dose Range (≤10 mg/day → discontinuation)

• This is the critical phase where most errors occur. 1
• Reduce by 1 mg every 4 weeks until discontinuation—faster tapering below 10 mg/day significantly increases relapse risk. 1, 7
• If 1-mg tablets are unavailable, use alternate-day dosing (e.g., 10 mg/7.5 mg on alternating days) to achieve gradual reductions. 1

Special Consideration: Patients on Steroid-Sparing Agents

• If the patient is already on azathioprine (established for ≥2–3 months), methotrexate, or mycophenolate, the taper can be accelerated above 10 mg/day: reduce by 5 mg weekly until 10 mg/day, then by 2.5 mg every 2–4 weeks. 1
• If no steroid-sparing agent is in place and multiple relapses occur, add azathioprine 2 mg/kg/day, methotrexate, or mycophenolate to facilitate successful tapering. 1

Ongoing Management and Prevention

Stress-Dosing Education

• All patients on chronic prednisone (>3 weeks at >7.5 mg/day) and for 6–12 months after discontinuation require stress-dosing protocols. 6, 3, 4
• During acute illness (fever, infection, gastroenteritis): double the current prednisone dose for 3 days. 1
• During major physiologic stress (surgery, severe infection): administer hydrocortisone 50–100 mg IV three times daily. 1
• Provide patients with injectable hydrocortisone 100 mg IM for emergency use and instruct them to seek immediate medical care if unable to take oral medication. 6, 4

Medical Alert Identification

• Patients should carry a medical-alert card or bracelet identifying them as at risk for adrenal insufficiency. 1, 4

Long-Term Monitoring

• Schedule follow-up visits every 4–8 weeks during the first year of tapering, then every 8–12 weeks in the second year. 1
• Monitor for signs of adrenal insufficiency (fatigue, orthostatic hypotension, weight loss, hyponatremia) and disease activity markers. 1, 6

Common Pitfalls to Avoid

• Tapering too quickly below 10 mg/day is the most common error and leads to disease flare or symptomatic adrenal insufficiency. 1
• Failing to distinguish between disease flare and adrenal insufficiency—both require different management strategies but can coexist. 1, 4
• Attempting diagnostic cortisol testing while on supraphysiologic prednisone doses—results are uninterpretable. 2
• Not providing stress-dosing education—adrenal crisis can be fatal if untreated. 3, 4
• Discontinuing prednisone based solely on symptom resolution without confirming HPA-axis recovery via cortisol testing. 1, 6