Review Question - QID 104416

This patient presents with hypercalcemia of malignancy. The first step in management is intravenous volume expansion with an isotonic solution such as normal saline.

There are a number of causes of hypercalcemia including:

(1) Endocrinopathies such as primary hyperparathyroidism (elevated PTH), renal failure (which usually results in hypocalcemia but may also result in secondary hyperparathyroidism and hypercalcemia), Paget's disease of the bone.
(2) Malignancies such as bony metastases from metastatic cancer and osteolytic or osteoblastic lesions, multiple myeloma, or tumors that release PTH-like hormone such as squamous cell lung cancer. All of these conditions of suppressed PTH levels.
(3) Pharmacologic causes such as Vitamin D intoxication, milk-alkali syndrome, and thiazide diuretics.
(4) Other causes such as familial hypocalciuric hypercalcemia and sarcoidosis (rare except on boards).

Clinical features include "stones, bones, groans, and psychiatric overtones", and treatment revolves around increasing urinary excretion of calcium and reducing intake or production. Intravenous fluids are the first step in management. Additional management considerations include bisphosphonates and calcitonin. Furosemide is sometimes used after IV volume expansion to facilitate calciuresis, though its role is less defined.

Carroll et al. discuss a practical approach to hypercalcemia. Clinical manifestations affect the neuromuscular, gastrointestinal, renal, skeletal, and cardiovascular systems. The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy.

Clines discusses mechanisms and treatment of hypercalcemia of malignancy. The vast majority of cases are caused by tumor-produced parathyroid hormone-related protein followed by infrequent tumor production of 1,25-dihydroxyvitamin D and parathyroid hormone. The remaining 20% of cases are caused by bone metastasis with consequent bone osteolysis and release of skeletal calcium.

Illustration A shows a classic EKG of hypercalcemia with a shortened QT interval. In contrast, in hypocalcemia, the QT may be prolonged.

Incorrect Answers:
Answer 1: Bisphosphonates are an effective treatment for hypercalcemia but take time to start working and are not the first step in management.
Answer 2: Calcitonin works faster than bisphosphonates but is not the first step in management.
Answer 3: Furosemide is an ancillary treatment option, but should never be given prior to intravenous volume expansion.
Answer 5: A thiazide diuretic should not be given as it could make hypercalcemia worse by increasing renal calcium reabsorption.