Which protein is most often elevated in hypercalcemia due to malignancy?

In cases of hypercalcemia related to malignancy, the protein that is most frequently elevated is parathyroid hormone-related protein (PTHRP). This protein is structurally similar to parathyroid hormone (PTH) and is produced by certain types of tumors, particularly those associated with squamous cell carcinomas of the lung and other cancers. PTHRP mimics the action of PTH, leading to increased osteoclastic bone resorption and enhanced renal tubular reabsorption of calcium, which contributes to the elevated levels of calcium in the blood.

The inappropriate secretion of PTHRP in malignancy highlights the pathological role of tumors in regulating calcium homeostasis, which can lead to significant clinical consequences, including symptoms related to high calcium levels such as nausea, vomiting, confusion, and increased thirst.

Understanding the role of PTHRP is crucial in distinguishing malignancy-related hypercalcemia from other forms of hypercalcemia, where mechanisms involve different proteins, such as PTH or calcitonin. This distinction is vital for appropriate management of patients exhibiting symptoms of hypercalcemia.