What is the most common malignancy causing hypercalcemia?

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Last updated: March 16, 2025View editorial policy

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From the Guidelines

Multiple myeloma is the most common malignancy causing hypercalcemia. Hypercalcemia of malignancy occurs in approximately 20-30% of cancer patients during the course of their disease 1. In multiple myeloma, the mechanism typically involves excess bone resorption from bone disease, leading to excessive release of calcium into the blood, contributing to hypercalcemia 1. Symptoms include polyuria and gastrointestinal disturbances, with progressive dehydration and decreases in glomerular filtration rate 1.

Treatment of Hypercalcemia

Treatment typically involves addressing the underlying malignancy while managing the hypercalcemia with:

  • Aggressive hydration
  • Bisphosphonates like zoledronic acid (4mg IV) or pamidronate (60-90mg IV) 1
  • Calcitonin (4-8 IU/kg SC/IM every 12 hours)
  • Denosumab (120mg SC) may be used in refractory cases or in patients with renal impairment where bisphosphonates are contraindicated 1

Prevention of Infections

To prevent infections in patients with multiple myeloma, the panel recommends referring to the NCCN Guidelines for Prevention and Treatment of Cancer-Related Infections and the CDC recommendations for Use of COVID-19 Vaccines in the United States 1.

Management of Venous Thromboembolism (VTE)

The highest risk for venous thromboembolism (VTE) is in the first 6 months after a new diagnosis of MM. The NCCN MM Panel has outlined management of VTE, risk stratification, and VTE prophylaxis in a separate section in the NCCN Guidelines for MM 1. Some key points to consider in the management of multiple myeloma and hypercalcemia include:

  • Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity 1
  • Erythropoietin therapy may be considered for patients with anemia, especially those with renal failure 1
  • Measuring endogenous erythropoietin levels may also be helpful in treatment planning 1

From the Research

Causes of Hypercalcemia

  • Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease 2
  • It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ 2
  • Breast cancer has the highest prevalence of hypercalcemia among all cancer in females 3

Prevalence of Hypercalcemia in Cancer Patients

  • Hypercalcemia occurs in approximately 10-30% of all patients with neoplastic disease 4
  • It is the most common life-threatening metabolic disorder associated with cancer 4
  • Hypercalcemia is most common in those who have later-stage malignancies and predicts a poor prognosis for those with it 5

Most Common Malignancy Causing Hypercalcemia

  • Breast cancer is the most common malignancy causing hypercalcemia, with approximately 70% of patients with breast cancer having bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease 3
  • Other common malignancies causing hypercalcemia include multiple myeloma, leukemia, and non-Hodgkins lymphoma, as well as solid cancers such as renal carcinomas and squamous cell carcinomas of any organ 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hypercalcemia of malignancy and new treatment options.

Therapeutics and clinical risk management, 2015

Research

Hypercalcemia of malignancy treated with cinacalcet.

Endocrinology, diabetes & metabolism case reports, 2017

Research

Hypercalcemia in cancer patients: pathobiology and management.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2010

Research

Cancer-Related Hypercalcemia.

Journal of oncology practice, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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