Hypercalcaemia of malignancy

Overview Of Hypercalcaemia of malignancy

Hypercalcemia of malignancy is a condition characterized by elevated levels of calcium in the blood, specifically as a result of cancer. It is one of the most common paraneoplastic syndromes, meaning it occurs in association with cancer, but not directly due to the tumor's spread or metastasis. This condition occurs when cancer cells either release substances that increase calcium levels or when bone metastases occur, leading to bone breakdown and the release of calcium into the bloodstream. Hypercalcemia of malignancy can be a life-threatening complication, often resulting from cancers such as lung cancer, breast cancer, multiple myeloma, or certain hematologic cancers. Symptoms of hypercalcemia can range from mild, such as fatigue and nausea, to severe, including confusion, kidney failure, and cardiac arrhythmias. Immediate management is necessary to prevent serious consequences.

Causes of Hypercalcaemia of malignancy

• Hypercalcemia of malignancy typically arises from several mechanisms associated with cancer: - Bone Metastasis: Cancers such as breast, lung, or prostate cancer can metastasize to the bones, causing increased osteoclastic activity. This results in the breakdown of bone tissue and the release of calcium into the bloodstream. - Tumor Production of Parathyroid Hormone-related Protein (PTHrP): Some cancers, especially squamous cell carcinomas of the lung, breast, or head and neck, secrete a protein called PTHrP, which mimics the action of parathyroid hormone (PTH). PTHrP promotes calcium release from the bones and increases calcium reabsorption from the kidneys. - Tumor Lysis Syndrome: In some cases, the rapid breakdown of tumor cells during chemotherapy (tumor lysis) can lead to the release of calcium into the bloodstream, causing hypercalcemia. - Increased Vitamin D Production: Some cancers, such as lymphomas, may cause overproduction of calcitriol, the active form of vitamin D. This leads to increased calcium absorption from the gastrointestinal tract. - Renal Dysfunction: Tumors may also impair kidney function, leading to reduced excretion of calcium and its accumulation in the blood. - Myeloma and Leukemia: Malignant blood disorders like multiple myeloma and some forms of leukemia can also lead to hypercalcemia by affecting bone metabolism and calcium regulation.

Risk Factors of Hypercalcaemia of malignancy

• The following factors increase the likelihood of developing hypercalcemia of malignancy: - Cancer Type: Certain cancers, particularly those with a propensity for bone metastasis or those that produce parathyroid hormone-related protein (PTHrP), are associated with a higher risk. Common cancers include lung cancer, breast cancer, multiple myeloma, renal cell carcinoma, and squamous cell carcinoma. - Bone Metastasis: Individuals with advanced cancer, particularly those with bone metastases, are at increased risk of developing hypercalcemia. - Lymphomas: Certain types of lymphoma, including Hodgkin and non-Hodgkin lymphoma, can increase the risk due to their ability to increase vitamin D production. - Tumor Lysis Syndrome: Cancer patients undergoing chemotherapy are at risk of tumor lysis syndrome, which can cause the release of intracellular calcium and result in hypercalcemia. - Advanced Disease Stage: Hypercalcemia is more commonly seen in the later stages of cancer, particularly when metastasis or extensive tumor burden occurs. - Dehydration: Dehydration, which is common in cancer patients, can exacerbate hypercalcemia by reducing kidney function and calcium clearance.

Prevention of Hypercalcaemia of malignancy

• While it may not be possible to prevent hypercalcemia of malignancy entirely, certain strategies can reduce the risk or mitigate its effects: - Early Detection of Cancer: Regular screenings and early diagnosis of cancers associated with hypercalcemia (e.g., breast cancer, lung cancer) can help manage the disease before complications arise. - Aggressive Cancer Treatment: Prompt and aggressive treatment of cancer, including the use of chemotherapy, targeted therapies, or radiation, can reduce tumor burden and prevent complications like bone metastases, which contribute to hypercalcemia. - Bone-Targeted Therapy: For cancers known to metastasize to bones, bisphosphonates or denosumab may be used as preventive therapy to reduce the risk of hypercalcemia by inhibiting bone resorption. - Hydration: Adequate hydration, particularly in cancer patients undergoing treatments that increase the risk of dehydration (e.g., chemotherapy), can help prevent the onset of hypercalcemia by ensuring proper renal calcium excretion. - Monitoring of Calcium Levels: Regular blood tests to monitor calcium levels in cancer patients, especially those with known risk factors, can allow for early detection and intervention of hypercalcemia.

Prognosis of Hypercalcaemia of malignancy

• The prognosis of hypercalcemia of malignancy depends largely on the severity of the hypercalcemia and the underlying cancer. When detected early and treated promptly, the majority of cases can be managed successfully with a combination of hydration, medications, and treating the underlying malignancy. However, severe, untreated hypercalcemia can be fatal, leading to organ dysfunction, renal failure, arrhythmias, or coma. The prognosis also depends on the type and stage of the cancer; patients with advanced or metastatic cancers often have a poorer prognosis, despite successful management of hypercalcemia.

Complications of Hypercalcaemia of malignancy

• If hypercalcemia of malignancy is not promptly treated, it can lead to several serious complications: - Renal Failure: High calcium levels can lead to kidney damage and failure due to the kidneys' inability to excrete excessive calcium. - Cardiac Arrhythmias: Elevated calcium levels can disrupt the normal electrical activity of the heart, leading to arrhythmias or even cardiac arrest. - Coma: In severe cases, confusion and cognitive impairment from high calcium levels can progress to coma. - Bone Fractures: Chronic hypercalcemia due to metastatic bone disease can weaken bones, increasing the risk of fractures. - Gastrointestinal Complications: Severe hypercalcemia can lead to significant gastrointestinal disturbances, including nausea, vomiting, and constipation, which can exacerbate dehydration and electrolyte imbalances.

Related Diseases of Hypercalcaemia of malignancy

• Conditions associated with hypercalcemia of malignancy include: - Hyperparathyroidism: A condition where the parathyroid glands produce too much parathyroid hormone, leading to elevated calcium levels. - Multiple Myeloma: A type of cancer that affects plasma cells in the bone marrow, often causing bone destruction and hypercalcemia. - Paget’s Disease of Bone: A chronic bone disorder that can sometimes lead to hypercalcemia due to abnormal bone resorption. - Vitamin D Toxicity: Excessive levels of vitamin D, often from supplementation or certain disorders, can lead to elevated calcium levels. - Bone Metastases: Many types of cancer, including breast and prostate cancers, can metastasize to bone, leading to hypercalcemia due to increased bone resorption.

Treatment of Hypercalcaemia of malignancy

The management of hypercalcemia of malignancy aims to lower calcium levels quickly and treat the underlying cancer. Treatment options include: - **Hydration**: Intravenous (IV) fluids, typically saline, are given to help increase renal calcium excretion and dilute the calcium in the bloodstream. - **Bisphosphonates**: Medications such as zoledronic acid or pamidronate inhibit osteoclast-mediated bone resorption, reducing calcium release from bones. - **Denosumab**: A monoclonal antibody that targets RANKL, a protein involved in osteoclast activity, denosumab can be used to inhibit bone resorption and treat hypercalcemia in malignancy. - **Calcitonin**: This hormone lowers calcium levels by inhibiting bone resorption and promoting calcium excretion through the kidneys. It can be used for short-term management of severe hypercalcemia. - **Corticosteroids**: For hypercalcemia caused by certain cancers, such as lymphoma, corticosteroids may be used to decrease calcium levels by reducing inflammation and inhibiting vitamin D activation. - **Dialysis**: In severe cases where calcium levels are life-threatening and refractory to other treatments, dialysis may be required to remove excess calcium from the bloodstream. - **Chemotherapy**: In cases where tumor burden is contributing to hypercalcemia, chemotherapy aimed at reducing the size of the tumor or metastasis may help lower calcium levels. - **Surgical Intervention**: In rare cases, if hypercalcemia is caused by a parathyroid adenoma or certain tumors that secrete parathyroid hormone, surgery may be necessary.