Hypercalcemia, an abnormally high level of calcium in the blood, is a frequent metabolic complication observed in individuals with cancer. Understanding why cancer leads to this elevation is important for recognition and intervention. This article explores the mechanisms by which malignancies disrupt the body’s calcium balance.
Calcium Regulation in the Body
The body maintains a precise balance of calcium, a mineral vital for functions like bone strength, muscle contraction, and nerve signaling. This balance, known as calcium homeostasis, involves bones, kidneys, and intestines. Bones serve as the primary reservoir, releasing calcium into the bloodstream and storing excess. The kidneys filter and reabsorb calcium, while the intestines absorb it from dietary sources.
Parathyroid hormone (PTH) and calcitriol (active vitamin D) are the primary hormones regulating blood calcium. PTH, released when calcium levels drop, promotes calcium release from bones, increases kidney reabsorption, and stimulates vitamin D activation. Calcitriol, produced in the kidneys, enhances calcium absorption from the intestines and influences bone and kidney calcium handling.
Cancer’s Methods of Elevating Calcium
Cancer can disrupt the body’s calcium regulation through several distinct mechanisms. These vary depending on the cancer type and stage.
Humoral Hypercalcemia of Malignancy (HHM)
Humoral hypercalcemia of malignancy (HHM) is the most common cause of cancer-related hypercalcemia, accounting for approximately 80% of cases. This mechanism involves tumors secreting parathyroid hormone-related protein (PTHrP). PTHrP mimics natural parathyroid hormone, binding to the same receptors in bones and kidneys. This mimicry increases bone breakdown, releasing calcium into the bloodstream, and signals kidneys to reabsorb more calcium, preventing its excretion.
Solid tumors like squamous cell carcinoma of the lung, head and neck cancers, breast cancer, kidney cancer, and ovarian cancer are frequently associated with HHM. Hematological malignancies such as non-Hodgkin lymphoma and leukemia can also cause HHM.
Local Osteolytic Hypercalcemia
Local osteolytic hypercalcemia occurs when cancer cells metastasize to bone, accounting for about 20% of cancer-related cases. Cancer cells in the bone directly stimulate osteoclasts, cells responsible for breaking down bone tissue. Increased osteoclast activity rapidly breaks down bone, releasing calcium into the bloodstream. This process is common in cancers that frequently spread to bone, including multiple myeloma, breast cancer, and lung cancer.
Other Less Common Mechanisms
Other less frequent mechanisms can also contribute to cancer-induced hypercalcemia. Some lymphomas can produce activated vitamin D, known as calcitriol. This ectopic production increases calcium absorption from the intestines and promotes bone resorption, leading to higher blood calcium levels.
Rarely, certain tumors may produce actual parathyroid hormone (PTH) instead of PTHrP. This ectopic PTH directly stimulates the same mechanisms as the body’s natural PTH, resulting in elevated blood calcium. Such cases are uncommon and require careful differentiation from primary hyperparathyroidism.
Why Understanding These Mechanisms Matters
Understanding how cancer causes hypercalcemia helps in accurately diagnosing elevated calcium levels in cancer patients. This guides healthcare professionals toward appropriate management strategies. Recognizing these mechanisms also helps predict which patients might be at higher risk for developing hypercalcemia based on their cancer type.
Hypercalcemia can manifest with symptoms including fatigue, weakness, nausea, vomiting, constipation, confusion, and increased thirst. More severe symptoms can involve kidney problems, heart rhythm abnormalities, and coma. Identifying the specific mechanism allows for targeted interventions to lower calcium levels and alleviate symptoms, improving patient comfort and outcomes.