How to manage a patient with hyperparathyroidism (primary overproduction of parathyroid hormone) and multiple myeloma (MM, a type of blood cancer)?

Management of Patients with Hyperparathyroidism and Multiple Myeloma

In patients with concurrent hyperparathyroidism and multiple myeloma, treatment should focus on controlling hypercalcemia with bisphosphonates or denosumab, while addressing both conditions separately to reduce morbidity and mortality. 1, 2

Initial Assessment and Diagnosis

• Differentiate between the two causes of hypercalcemia by measuring parathyroid hormone (PTH) levels (elevated in primary hyperparathyroidism) and conducting serum protein electrophoresis to identify monoclonal proteins from multiple myeloma 3
• Evaluate renal function through creatinine clearance, as both conditions can cause renal impairment 1
• Assess for bone disease through appropriate imaging (CT or MRI) to identify both lytic lesions from MM and bone changes from hyperparathyroidism 1
• Check for hypercalcemia-related symptoms including polyuria, gastrointestinal disturbances, dehydration, and decreased glomerular filtration rate 1

Management of Hypercalcemia

Acute Management

• Provide aggressive hydration as first-line treatment for hypercalcemia from either cause 1, 4
• Administer bisphosphonates, with zoledronic acid being the preferred agent for hypercalcemia treatment in MM patients 1
• Consider calcitonin as a temporary measure for severe symptomatic hypercalcemia while other treatments take effect 4

Chronic Management

• For patients with both conditions who are poor surgical candidates or refuse surgery for hyperparathyroidism, medical management with cinacalcet (a calcimimetic) and bisphosphonates is recommended 2
• Ensure calcium and vitamin D3 supplementation for all patients receiving intravenous bisphosphonates to prevent hypocalcemia 1
• Monitor renal function closely by measuring creatinine clearance, serum electrolytes, and urinary albumin in all patients receiving bisphosphonate therapy 1

Multiple Myeloma-Specific Management

• Continue bone-targeting treatment (bisphosphonates or denosumab) for up to 2 years in MM patients; continuation beyond 2 years should be based on clinical judgment 1
• Denosumab is preferred in patients with renal disease 1
• For MM patients with painful osteolytic lesions, consider radiotherapy (30 Gy in 10-15 fractions) 1
• Consider balloon kyphoplasty for management of painful vertebral compression fractures 1

Hyperparathyroidism-Specific Management

• Surgical removal of parathyroid adenoma/hyperplasia (parathyroidectomy) remains the definitive treatment for primary hyperparathyroidism when feasible 5, 3
• In patients who cannot undergo surgery due to MM-related complications or other contraindications, medical management with cinacalcet and bisphosphonates is appropriate 2

Special Considerations

• Renal function monitoring is critical as both conditions can cause renal impairment; adjust bisphosphonate dosing accordingly 1
• For patients with creatinine clearance 30-60 mL/min, use reduced doses of zoledronic acid with no change to infusion time 1
• For patients with creatinine clearance <30 mL/min, avoid pamidronate and zoledronic acid; consider clodronate if creatinine clearance is >12 mL/min 1
• Perform baseline dental examination and monitor for osteonecrosis of the jaw (ONJ) in all patients receiving bone-modifying agents 1
• If ONJ develops, discontinue bisphosphonates until healing occurs 1

Follow-up Recommendations

• Monitor calcium levels regularly to assess treatment efficacy 4
• Evaluate renal function regularly, especially in patients receiving bisphosphonates 1
• Assess response to MM therapy through standard criteria 1
• Screen for monoclonal gammopathy in patients with primary hyperparathyroidism, as evidence suggests monoclonal gammopathies occur more often in these patients than in the general population 3

Pitfalls to Avoid

• Do not assume hypercalcemia is due to only one condition when both are present; treatment may need to target both pathologies 6
• Hypophosphatemia in a patient with MM and hypercalcemia should raise suspicion for concurrent hyperparathyroidism 6
• Avoid delaying systemic anti-myeloma therapy for radiation therapy; they can often be given concurrently with careful monitoring for toxicities 1
• Be aware that hypercalcemia may be difficult to control when both conditions are present and may require combination therapy 6