What is the appropriate workup for a patient with Cushing's syndrome suspected of having gouty arthritis?

Workup for Gouty Arthritis in a Patient with Cushing's Syndrome

The workup for suspected gouty arthritis requires synovial fluid aspiration with crystal analysis as the definitive diagnostic test, combined with assessment of secondary causes of hyperuricemia—particularly important in Cushing's syndrome, which is a known risk factor for hyperuricemia. 1

Definitive Diagnostic Testing

Joint aspiration with synovial fluid analysis for monosodium urate (MSU) crystals under polarized light microscopy is mandatory and should be attempted in every patient with suspected gout. 1, 2, 3

• MSU crystals appear as needle-shaped, negatively birefringent crystals with sensitivity of 63-78% and specificity of 93-100% when performed by experienced operators 2, 4, 3
• Always perform Gram stain and culture even when MSU crystals are identified, as gout and septic arthritis can coexist 2, 3
• This is particularly critical because clinical algorithms alone cannot reliably exclude septic arthritis 2

Clinical Assessment

When joint aspiration is not immediately feasible, document these high-value clinical features that support gout diagnosis:

• Rapid onset of severe pain reaching maximum intensity within 6-24 hours (odds ratio 3.58 for gout) 1, 2, 4
• Monoarticular involvement of the first metatarsophalangeal joint (podagra) with odds ratio 7.29 1, 2, 4
• Visible tophi on physical examination (odds ratio 7.29) 4
• Overlying erythema with severe tenderness 1, 2, 4
• History of previous similar acute episodes 1, 2

However, these clinical features have 98% sensitivity but only 23% specificity, meaning they cannot definitively confirm gout without crystal identification. 3

Laboratory Investigations

Serum Uric Acid

• Measure serum uric acid level, but do not make the diagnosis based on hyperuricemia alone 1, 4
• Only 22% of patients with uric acid >9 mg/dL develop gout within 5 years 4
• Normal serum uric acid essentially rules out gout in the clinical context 2

Assessment for Secondary Causes (Critical in Cushing's Syndrome)

In patients with Cushing's syndrome, systematically evaluate these secondary causes and risk factors for hyperuricemia: 1

• Medications that induce hyperuricemia: corticosteroids (intrinsic to Cushing's), diuretics, low-dose aspirin, cyclosporine, tacrolimus 1, 2
• Renal function: obtain serum creatinine and calculate GFR, as chronic kidney disease increases gout risk 4.95-fold 1, 2, 3
• Cardiovascular comorbidities: hypertension (relative risk 3.93), coronary heart disease, heart failure 1, 2, 3
• Metabolic factors: obesity (relative risk 3.81), diabetes, dyslipidemia 1, 2, 3

Additional Laboratory Tests

• 24-hour urine collection for urinary free cortisol excretion if Cushing's syndrome diagnosis needs confirmation 5, 6
• Fasting glucose and lipid panel to assess metabolic syndrome components 3

Imaging Studies (When Aspiration Not Feasible)

If joint aspiration cannot be performed or is technically difficult, use advanced imaging to detect MSU crystal deposition: 1, 2

First-Line Imaging: Ultrasound

• Look for the "double contour sign" at cartilage surfaces (sensitivity 74%, specificity 88%) 1, 2, 4
• Detect tophi not evident on clinical examination (sensitivity 65%, specificity 80%) 2
• Always include the first metatarsophalangeal joint in imaging regardless of whether it is symptomatic 2
• Ultrasound performs better in disease duration >2 years (63% sensitivity) versus <2 years (50% sensitivity) 2, 4

Second-Line Imaging: Dual-Energy CT (DECT)

• Use when ultrasound is inconclusive and disease duration >2 years 2
• Sensitivity 85-100%, specificity 83-92% for detecting MSU crystal deposits 1, 2, 4
• Less sensitive in early disease or shorter history of flares 2

Plain Radiographs

• Limited value for diagnosing acute gout flares 1, 2
• Useful only for identifying chronic structural damage and ruling out alternative diagnoses 2

Clinical Algorithm When Aspiration Is Unavailable

If joint aspiration is truly not possible, a clinical diagnosis requires multiple features present together to achieve >80% sensitivity and specificity: 2, 4

• More than one previous attack of acute arthritis
• Maximum inflammation developing within 1 day
• Redness observed over the affected joint
• First metatarsophalangeal joint involvement
• Proven or suspected tophi
• Hyperuricemia present

This algorithm performs better in patients with disease duration >2 years than in recent-onset symptoms ≤2 years. 4

Critical Pitfalls to Avoid

• Never diagnose gout based on hyperuricemia alone—this has only 53-61% specificity 1, 2
• Do not skip joint aspiration when septic arthritis cannot be clinically excluded, as the relatively low specificity of clinical algorithms raises risk for missed septic arthritis 2
• Do not rely on imaging alone—integrate patient history, physical examination, and laboratory findings 2
• In Cushing's syndrome patients, consider eliminating non-essential medications that induce hyperuricemia (particularly diuretics if blood pressure control allows) 1

When to Refer to Specialist

Consider rheumatology referral for: 1

• Unclear etiology of hyperuricemia despite workup
• Refractory signs or symptoms of gout
• Difficulty reaching target serum urate with renal impairment
• Multiple or serious adverse events from urate-lowering therapy