Review Question - QID 104498

PTH-related peptide is associated with squamous cell carcinoma of the lung, renal cell carcinoma, and breast carcinoma. It causes hypercalcemia of malignancy. Patients with von Hippel-Lindau disease, are at high risk for renal cell carcinoma which can secrete PTH-related peptide causing hypercalcemia.

The syndrome of von Hippel-Lindau is marked by hemangioblastomas of the retina, cerebellum, and medulla and a high risk of bilateral renal cell carcinoma. The disease is associated with the deletion of the VHL tumor suppressor on chromosome 3p. This genetic abnormality causes constitutive expression of hypoxia inducible factor (HIF) and activation of angiogenic factors. Hypercalcemia of malignancy may be divided into hypercalcemia caused by blastic lesions and by paraneoplastic production of PTH-related peptide which functions similarly to PTH. PTH-related peptide can be released by squamous cell lung cancer, breast cancer, and renal cell carcinoma.

Carroll and Schade discuss a practical approach to hypercalcemia. The diagnosis is often made incidentally in asymptomatic patients. Clinical symptoms include muscle and bone pains, kidney stones, and mood changes. Parathyroid hormone is suppressed in malignancy-associated hypercalcemia and elevated in primary hyperparathyroidism. In patients with severe hypercalcemia, the first step in management is intravenous rehydration.

Radvanyi et al. discuss the importance of early diagnosis in hypercalcemia of malignancy. Cancer-related hypercalcemia may occur in 20%-30% of patients with cancer during the course of the disease. Cancer cells stimulate osteoclasts to resorb bone and stimulate calcium reabsorption at the renal tubules resulting in an elevation of serum calcium.

Figure A depicts a shortened QT interval as seen in hypercalcemia. Figure B is an abdominal CT scan demonstrating RCC.

Illustration A depicts retinal angiomas as seen in von Hippel-Lindau.

Incorrect Answers:
Answer 1: Primary hyperparathyroidism could cause hypercalcemia but would be less likely than PTH-related peptide given this patient's history of von Hippel-Lindau disease and risk of bilateral renal cell carcinoma.
Answer 3: An abnormality in chromosome 3 is the culprit in von Hippel-Lindau disease not chromosome 4.
Answer 4: Renal failure would cause hyperkalemia. However, the patient's EKG is indicative of hypercalcemia.
Answer 5: Acidemia may cause hyperkalemia as a result of the H+/K+ exchanger. However, it would not cause hypercalcemia.