Hypercalcemia of malignancy

Hypercalcemia of Malignancy

Hypercalcemia of malignancy is a condition characterized by elevated levels of calcium in the blood, which is often associated with cancer. It is a common paraneoplastic syndrome and can occur in various types of malignancies.

Pathophysiology

Hypercalcemia of malignancy can occur through several mechanisms:

• Humoral Hypercalcemia of Malignancy (HHM): This is the most common mechanism and is caused by the secretion of parathyroid hormone-related peptide (PTHrP) by the tumor. PTHrP mimics the action of parathyroid hormone (PTH), leading to increased bone resorption and renal tubular reabsorption of calcium.

• Osteolytic Metastases: Certain cancers, such as breast cancer and multiple myeloma, can metastasize to bone, causing local osteolysis and release of calcium into the bloodstream.

• Vitamin D Secretion: Some lymphomas can produce active vitamin D (calcitriol), leading to increased intestinal absorption of calcium.

Clinical Presentation

Patients with hypercalcemia of malignancy may present with a variety of symptoms, which can be remembered by the mnemonic "stones, bones, groans, and psychiatric overtones":

• Renal: Nephrolithiasis (kidney stones), polyuria, and dehydration.
• Skeletal: Bone pain and fractures.
• Gastrointestinal: Nausea, vomiting, constipation, and abdominal pain.
• Neurological: Confusion, lethargy, and in severe cases, coma.

Diagnosis

The diagnosis of hypercalcemia of malignancy involves:

• Serum Calcium Levels: Elevated total and ionized calcium levels.
• Parathyroid Hormone (PTH) Levels: Typically low or suppressed in hypercalcemia of malignancy.
• PTHrP Levels: Elevated in cases of humoral hypercalcemia of malignancy.
• Bone Scans and Imaging: To identify osteolytic lesions or metastases.

Treatment

The management of hypercalcemia of malignancy includes:

• Hydration: Intravenous fluids to promote renal excretion of calcium.
• Bisphosphonates: Such as zoledronic acid or pamidronate, to inhibit bone resorption.
• Calcitonin: Provides a rapid but short-term reduction in calcium levels.
• Denosumab: A monoclonal antibody that inhibits RANKL, used in cases refractory to bisphosphonates.
• Glucocorticoids: Particularly effective in cases of vitamin D-mediated hypercalcemia.
• Dialysis: In severe cases where other treatments are ineffective.

Prognosis

The prognosis of hypercalcemia of malignancy is generally poor, as it often indicates advanced disease. The condition requires prompt treatment to prevent complications and improve quality of life.

See Also

• Paraneoplastic syndrome
• Multiple myeloma
• Breast cancer
• Lymphoma

External Links

• [American Cancer Society](https://www.cancer.org/)
• [National Cancer Institute](https://www.cancer.gov/)