What substance secreted by neoplastic T-cells is responsible for hypercalcemia in lymphoma dogs?

The substance responsible for hypercalcemia in dogs with lymphoma is parathyroid hormone-related peptide (PTHrP). This peptide mimics the action of parathyroid hormone, leading to increased calcium levels in the bloodstream. In certain types of malignancies, particularly those involving T-cells, PTHrP is produced ectopically, contributing to a condition known as humoral hypercalcemia of malignancy.

This phenomenon occurs when tumor cells, in this case from lymphoma, secrete PTHrP, prompting the bones to release calcium into the circulation. The increase in serum calcium can lead to a variety of clinical signs, including lethargy, gastrointestinal disturbances, and renal issues. Understanding the mechanism of action and the pathophysiology of this condition is crucial. It's noteworthy that while other substances like calcitonin, parathyroid hormone, and vitamin D play roles in calcium metabolism, they do not typically cause the hypercalcemia associated with lymphoma in dogs, making PTHrP the key substance in this scenario.