**Question:** Immediate treatment of hypercalcemia of malignancy is

A. Vitamin D receptor activator (e.g., calcimimetics)
B. Glucocorticoids
C. Hyperhydration and IV bisphosphonates
D. Intravenous hydration and furosemide

**Correct Answer:** C. Hyperhydration and IV bisphosphonates

**Core Concept:** Hypercalcemia of malignancy (HCM) is a paraneoplastic syndrome that occurs due to the production of parathyroid hormone-related protein (PTHrP) by malignant cells. This leads to increased calcium reabsorption in the kidneys and increased calcium release from bones, causing hypercalcemia.

**Why the Correct Answer is Right:** The correct answer, hyperhydration and intravenous bisphosphonates, addresses both the renal and bone-related causes of hypercalcemia in HCM. Bisphosphonates are a class of medications that inhibit osteoclast activity and decrease calcium release from bones. Hyperhydration helps flush calcium out of the kidneys and reduce calcium reabsorption.

**Why Each Wrong Option is Incorrect:**

A. Vitamin D receptor activator (e.g., calcimimetics) like cinacalcet targets calcium-sensing receptors (CaSR) on the parathyroid gland, not the renal and bone causes of HCM.

B. Glucocorticoids, like prednisolone, are used to suppress the immune system but do not address the renal and bone causes of HCM.

D. Intravenous hydration and furosemide (a loop diuretic) is used to reduce the extracellular fluid volume, but does not target the renal and bone causes of HCM. Furosemide does not have a direct effect on calcium reabsorption or bone resorption.

**Clinical Pearl:** Hypercalcemia of malignancy can lead to severe complications, including nephrolithiasis, nephrocalcinosis, and renal insufficiency. Early and appropriate management is crucial to prevent these complications and improve patient outcomes.