The two most common causes of hypercalcemia are primarily which conditions?

Hypercalcemia is defined as an elevated level of calcium in the blood, and its most common causes are indeed hyperparathyroidism and malignancy.

Hyperparathyroidism leads to excess secretion of parathyroid hormone (PTH), which increases calcium levels by mobilizing calcium from bones, enhancing intestinal absorption of calcium, and reducing renal excretion of calcium. This condition is frequently caused by parathyroid adenomas, hyperplasia, or, in some cases, malignancies that produce parathyroid hormone-related peptide (PTHrP), which mimics PTH action and raises calcium levels.

Malignancy contributes to hypercalcemia through several mechanisms, particularly osteolytic metastases from cancers such as breast, lung, and multiple myeloma, which directly invade bone and release calcium into the bloodstream. Additionally, solid tumors can produce PTHrP, again contributing to the hypercalcemic state.

In contrast, other conditions listed do not primarily lead to hypercalcemia. Hypoparathyroidism is characterized by low calcium levels due to insufficient parathyroid hormone. Vitamin D deficiency typically results in hypocalcemia because it impairs calcium absorption from the gut. Hypocalcemia and renal disease do not induce hypercalcemia;