How is pseudogout associated with hyperparathyroidism typically managed?

Pseudogout and Hyperparathyroidism: Association and Management

The Critical Association

Patients with calcium pyrophosphate deposition disease (CPPD/pseudogout) are three times more likely to have primary hyperparathyroidism than patients without CPPD (OR=3.03), and treatment of the underlying hyperparathyroidism is required, though whether this improves the arthritis outcome remains unclear. 1

Understanding the Relationship

• Primary hyperparathyroidism predisposes to CPPD crystal formation through chronic hypercalcemia and altered calcium-phosphate metabolism, creating an environment favorable for calcium pyrophosphate crystal deposition in joints 1

• Conversely, patients with primary hyperparathyroidism may have an increased risk of acute attacks of CPP arthritis 1

• The association is strong enough that screening for hyperparathyroidism should be performed in patients presenting with CPPD 1

Management Algorithm

Step 1: Diagnose Both Conditions

• Confirm CPPD through joint aspiration showing calcium pyrophosphate dihydrate crystals with weakly positive birefringence on polarized light microscopy 2, 3, 4

• Diagnose hyperparathyroidism with elevated or high-normal intact PTH in the setting of elevated serum calcium 5

• Screen for chondrocalcinosis with preoperative radiological studies of knees, wrists, and pelvis before any parathyroid surgery 2, 6

Step 2: Treat the Acute Pseudogout Attack

• NSAIDs are first-line for acute CPP crystal arthritis 1

• Colchicine 1 mg/day orally effectively suppresses acute attacks 2

• Intra-articular corticosteroid injection for monoarticular involvement 1

• Low-dose oral corticosteroids for polyarticular disease, though this recommendation is based on expert opinion alone 1

Step 3: Definitive Treatment of Hyperparathyroidism

• Parathyroidectomy is the definitive treatment for primary hyperparathyroidism and is typically indicated even when asymptomatic, given potential negative effects of long-term hypercalcemia 5

• Minimally invasive parathyroidectomy (MIP) is preferred when a single adenoma is confidently localized preoperatively (appropriate for approximately 80% of patients) 5

• Bilateral neck exploration (BNE) is required for discordant or nonlocalizing imaging or when multigland disease is suspected 5

Step 4: Prevent Post-Parathyroidectomy Pseudogout Crisis

This is the most critical pitfall to avoid: Acute pseudogout attacks frequently develop within 48 hours after parathyroidectomy due to rapid drops in serum calcium 2, 6, 3

Prevention protocol:

• Start prophylactic colchicine 1 mg/day orally before surgery in patients with known chondrocalcinosis 2

• Initiate calcium supplement therapy on postoperative day 1 to prevent sudden decreases in serum calcium concentration 6

• Monitor ionized calcium every 4-6 hours for the first 48-72 hours after surgery, then twice daily until stable 1

• Maintain calcium infusion if ionized calcium falls below 0.9 mmol/L (3.6 mg/dL), using calcium gluconate at 1-2 mg elemental calcium per kg body weight per hour 1

• Transition to oral calcium carbonate 1-2 g three times daily plus calcitriol up to 2 μg/day when oral intake is possible 1

Long-Term Management Considerations

• No definitive treatment exists to prevent CPP crystal formation or enhance dissolution, unlike urate crystals in gout 1

• Whether treating hyperparathyroidism improves CPPD outcomes is unclear, though treatment of the comorbidity is obviously required 1

• Magnesium supplementation has theoretical benefits for CPP crystal dissolution based on in vitro studies, but one small RCT showed no reduction in radiographic chondrocalcinosis despite possible clinical benefits 1

Special Clinical Scenarios

Gout can also occur with hyperparathyroidism: Serum uric acid levels positively correlate with serum iPTH levels, and parathyroidectomy leads to reduction in uric acid levels 7

Septic arthritis can mimic pseudogout flare: In patients with known CPPD and hyperparathyroidism presenting with acute monoarticular arthritis, always perform Gram stain and culture even when CPPD crystals are present, as bacterial infection can precipitate acute pseudogout 4