What is the optimal management of an acute gout flare in a patient with primary adrenal insufficiency (Addison’s disease) on adrenal replacement therapy?

Managing Acute Gout Flare in Addison's Disease

Direct Recommendation

Use systemic corticosteroids as first-line therapy for acute gout flares in patients with Addison's disease on stable replacement therapy, as they are already receiving glucocorticoid replacement and corticosteroids are as effective as NSAIDs with fewer adverse effects. 1

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Treatment Algorithm

First-Line: Systemic Corticosteroids

For patients already on stable adrenal replacement therapy:

• Continue their baseline hydrocortisone replacement dose (typically 15-25 mg daily in divided doses) 2
• Add stress-dose glucocorticoids by doubling or tripling the usual daily dose for the duration of the acute gout flare 2
• Typical approach: If on hydrocortisone 20 mg daily (10 mg AM, 5 mg noon, 5 mg afternoon), increase to 40-60 mg daily in divided doses during the flare 2
• Alternative: Prednisolone 35 mg daily for 5 days has been successfully used for acute gout 1

Critical advantage: Patients with Addison's disease require stress-dose steroids during any acute illness or inflammatory condition, so treating the gout flare simultaneously addresses both the inflammatory arthritis and the physiologic stress response 2, 3

Why NSAIDs Are Problematic

• NSAIDs can interfere with fludrocortisone (the mineralocorticoid replacement these patients require) 4
• NSAIDs may be contraindicated in patients with renal disease, heart failure, or cirrhosis—conditions that may coexist with adrenal insufficiency 1
• Risk of gastrointestinal bleeding is concerning, especially given that adrenal crisis can present with abdominal pain and vomiting, potentially masking NSAID-related complications 5, 3

Colchicine Considerations

Colchicine can be used but requires caution:

• Low-dose regimen: 1.2 mg followed by 0.6 mg one hour later (total 1.8 mg) 1
• Avoid in renal or hepatic impairment when using potent CYP3A4 inhibitors or P-glycoprotein inhibitors 1, 6
• Main advantage: Does not interfere with adrenal replacement therapy 6
• Main disadvantage: Gastrointestinal side effects (diarrhea, nausea, vomiting) can mimic early adrenal crisis, potentially delaying recognition of a life-threatening complication 1, 5, 6

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Critical Monitoring During Gout Flare

Watch for Adrenal Crisis

Any acute illness, including gout, can precipitate adrenal crisis in patients with Addison's disease: 5, 3

• Monitor for: Severe nausea/vomiting, abdominal pain, hypotension, confusion, or inability to take oral medications 5, 3
• If vomiting prevents oral intake: Immediately administer hydrocortisone 100 mg IV or IM and seek emergency care 5
• Patient education: Ensure the patient knows to use their emergency injectable hydrocortisone kit if they cannot keep oral medications down 2, 5

Electrolyte Monitoring

• Check sodium and potassium if the patient appears volume depleted or has persistent vomiting 5, 4
• Hyponatremia is present in 90% of adrenal crises, though hyperkalemia occurs in only ~50% 2, 5

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Common Pitfalls to Avoid

Never Delay Stress-Dose Steroids

The acute inflammatory stress of a gout flare requires increased glucocorticoid dosing—failure to increase the dose can precipitate adrenal crisis. 2, 3, 7

• Patients with Addison's disease cannot mount an endogenous cortisol response to stress 2, 8
• Even "minor" illnesses require dose adjustment 2, 3

Avoid Medication Interactions

• Do not use NSAIDs if the patient is on fludrocortisone, as NSAIDs interfere with mineralocorticoid activity 4
• Avoid grapefruit juice and licorice during treatment, as they decrease hydrocortisone clearance and may cause relative overdosing 2, 4

Recognize Gastrointestinal Symptoms

Nausea, vomiting, and abdominal pain can indicate either:

1. Colchicine side effects (common, dose-related) 1, 6
2. Early adrenal crisis (life-threatening) 5, 3

If in doubt, treat as adrenal crisis first—give parenteral hydrocortisone immediately and do not delay for diagnostic confirmation. 5

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Long-Term Urate-Lowering Therapy

Do not initiate urate-lowering therapy during the acute flare. 1

• After resolution: Discuss benefits and harms of long-term urate-lowering therapy if the patient has recurrent gout (≥2 episodes per year) 1
• Allopurinol is first-line when indicated, starting at low doses and titrating gradually 1
• No special precautions are needed for urate-lowering therapy in patients with stable adrenal insufficiency 1

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Patient Education Essentials

Every patient with Addison's disease must understand:

• Double or triple glucocorticoid dose during any acute illness, including gout flares 2, 3
• Wear medical alert identification at all times 2, 5
• Carry emergency injectable hydrocortisone (100 mg IM kit) and know how to use it 2, 5
• Seek immediate medical attention if unable to keep oral medications down or if symptoms worsen despite increased dosing 5, 3