In hypercalcemia, which scenario indicates a PTH-independent etiology such as malignancy?

• A. PTH-independent causes like malignancy or vitamin D intoxication.
• B. PTH-dependent causes such as primary hyperparathyroidism.
• C. Secondary hyperparathyroidism.
• D. Hypoparathyroidism.

Answer: (A)

In hypercalcemia, you distinguish causes by the PTH level. If calcium is high but PTH is appropriately or inappropriately elevated, the hypercalcemia is PTH-dependent, driven by excess PTH or PTH-like activity. If calcium is high with suppressed PTH, the cause is PTH-independent.

Malignancy fits this PTH-independent pattern because tumors can raise calcium through mechanisms such as secretion of PTH-related peptide or osteolytic bone resorption, which do not involve an increase in PTH. The elevated calcium then feeds back to suppress endogenous PTH.

The other scenarios involve PTH-dependent or different calcium-PTH relationships: primary hyperparathyroidism causes high PTH and hypercalcemia; secondary hyperparathyroidism features high PTH with usually low or normal calcium; hypoparathyroidism leads to low PTH with low calcium. Hence, describing PTH-independent etiologies such as malignancy best identifies the correct concept.