humoral hypercalcemia of malignancy (HHM) - Cancer Science

What is HHM?

Humoral Hypercalcemia of Malignancy (HHM) is a paraneoplastic syndrome characterized by elevated levels of calcium in the blood, which is often seen in patients with cancer. It occurs due to the secretion of hormones or hormone-like substances by malignant tumors. This condition is most commonly associated with cancers of the lung, breast, and certain types of hematologic malignancies.

What Causes HHM?

The primary cause of HHM is the secretion of parathyroid hormone-related protein (PTHrP) by the tumor cells. PTHrP mimics the action of parathyroid hormone, leading to increased bone resorption and renal tubular calcium reabsorption, which results in elevated blood calcium levels. Other factors that can contribute include increased production of Vitamin D analogs by lymphomas and the direct osteolytic activity of bone metastases.

What are the Symptoms of HHM?

Symptoms of HHM can vary depending on the severity of hypercalcemia. Common symptoms include nausea and vomiting, polyuria (increased urine output), polydipsia (increased thirst), constipation, abdominal pain, and fatigue. Severe cases may present with neurological symptoms like confusion, lethargy, and in extreme cases, coma.

How is HHM Diagnosed?

The diagnosis of HHM involves a combination of clinical assessment and laboratory tests. Serum calcium levels are measured, and elevated levels are indicative of hypercalcemia. Additional tests may include measuring serum PTHrP levels, serum parathyroid hormone (PTH) levels, and renal function tests. Imaging studies like bone scans and X-rays may be used to identify the presence of bone metastases.

What are the Treatment Options for HHM?

The primary goal in treating HHM is to lower the serum calcium levels and address the underlying malignancy. Treatment options include:

Intravenous (IV) fluids to promote renal calcium excretion.
Bisphosphonates to inhibit bone resorption.
Calcitonin for its rapid but short-term effect in lowering calcium levels.
Glucocorticoids to reduce intestinal calcium absorption and decrease Vitamin D production.
Dialysis in cases of severe hypercalcemia unresponsive to other treatments.

What is the Prognosis for Patients with HHM?

The prognosis of HHM largely depends on the type and stage of the underlying cancer. While the management of hypercalcemia can improve symptoms and quality of life, the presence of HHM often indicates advanced disease and a poorer prognosis. Early detection and treatment of the underlying malignancy are crucial for improving outcomes.

How Can HHM be Prevented?

Prevention of HHM involves regular monitoring of serum calcium levels in patients with known malignancies, particularly those at higher risk. Early intervention at the first signs of hypercalcemia can prevent the condition from becoming severe. Oncologists should remain vigilant for symptoms of hypercalcemia in their patients and consider HHM in differential diagnoses.