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Tumor lysis syndrome
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Excess calcium consumption
Excess vitamin D consumption
Paraneoplastic syndrome
Renal failure
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This patient has malignant hypercalcemia, secondary to the paraneoplastic syndrome of parathyroid related peptide (PTHrP) release by his squamous cell carcinoma. There are several causes of malignant hypercalcemia, but the most common cause is the production of PTHrP. PTHrP is a protein in the parathyroid hormone (PTH) family that is structurally similar to the PTH. PTHrP is able to bind and activate the PTH receptor, leading to increased bone resorption, kidney Ca reabsorption and ultimately, hypercalcemia. PTHrP is known to be secreted by squamous cell cancers of several organs, including: lungs, breast, esophagus, ovaries, bladder, and kidneys. Other causes of malignant hypercalcemia include ectopic PTH production, direct calcium release from bone lytic lesions, and excess vitamin D production. Carroll and Schade discuss the diagnostic approach to hypercalcemia in the primary care setting. It is typically an incidental finding. The most common causes are primary hyperparathyroidism and malignancy. Additionally, a hypercalcemic crisis should be managed with IV hydration, along with antiresorptive agents. Hastings et al. studied the expression of PTHrP by non-small cell lung carcinomas to determine its impact on survival. In a study of 407 patients, they found a statistically significant survival benefit in females whose tumors expressed PTHrP. Survival in men appeared to be unaffected by PTHrP expression. Illustration A shows a chest x-ray of a patient with advanced lung cancer. Incorrect Answers: Answer 1: Tumor lysis syndrome results from the destruction of tumor cells (often in the setting of chemotherapy initiation) and the subsequent release of intracellular contents. The HYPOcalcemia of tumor lysis syndrome is typically accompanied by other electrolyte abnormalities (e.g. hyperkalemia). Answer 2: Dietary consumption of calcium is insufficient to cause hypercalcemia without other predisposing factors (e.g. renal failure, excess PTH, vitamind D excess, etc). Answer 3: While excess vitamin D can cause hypercalcemia, in a patient with a known malignancy, a paraneoplastic syndrome is much more likely. Answer 5: Renal failure is more likely to lead to hypocalcemia due to decreased production of the active form of vitamin D.
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