Hypercalcemia from increased 1,25-OH D3 is typically associated with which condition?

Hypercalcemia due to increased levels of 1,25-dihydroxyvitamin D3 (1,25-OH D3) is often associated with certain types of malignancies, particularly lymphomas. In this context, lymphomas, especially some types of non-Hodgkin lymphoma, can lead to the production of calcitriol (1,25-OH D3) by the tumor cells. This increase in 1,25-OH D3 can result in enhanced intestinal absorption of calcium, increased renal tubular reabsorption of calcium, and mobilization of calcium from the bones, ultimately leading to hypercalcemia.

This mechanism of hypercalcemia is distinct from other malignancies where hypercalcemia occurs through different pathways, such as osteolytic metastasis (as seen in multiple myeloma or breast cancer) or through parathyroid hormone-related peptide (PTHrP) secretion in certain cancers. Renal cell carcinoma may also cause hypercalcemia but typically through different mechanisms such as bone involvement rather than by increasing 1,25-OH D3 production.

Hence, when looking for conditions specifically linked to hypercalcemia through increased 1,25-OH D3, lymphoma is the most relevant choice