Question 33

Question:

A 55-year-old female presents to her physician with mild fatigue. Past medical history is unremarkable. She is taking no medication. No abnormalities are detected on physical examination. The only abnormality detected on routine blood testing is an elevated calcium of 11.9 mg/dL and a serum inorganic phosphorus of 2 mg/dL. An immunoreactive parathyroid hormone level is undetectable. What is the most likely etiology of the patient’s high serum calcium?

Correct Answer: B.  Malignancy

Patients who present with hypercalcemia and hypophosphatemia should be thought of as having an excess of parathyroid hormone activity. Patients with nonparathyroid hormone–like mediated hypercalcemia, such as those with excessive levels of vitamin D caused by intoxication or sarcoidosis or by increased bone turnover as in hyperthyroidism, would not be expected to have a low serum phosphate. Patients with familial hypocalciuric hypercalcemia, an autosomal dominant trait, often have normal or slightly low levels of immunoreactive parathyroid hormone. Thus, those with hypercalcemia and hypophosphatemia without elevated levels of parathyroid hormone are likely to have the hypercalcemia of malignancy. The clinical setting usually but not invariably makes this diagnosis obvious. It is clearly recognized that many solid tumors, including carcinomas of the lung and kidney, may produce a parathyroid hormone–related protein that will not be identified by the currently available assays that detect true parathyroid hormone elaborated from the parathyroid gland. This parathyroid-related protein synthesized by tumors bears striking amino acid homology to that of native parathyroid hormone with regard to amino acids 1 through 13 but is thereafter unique. In fact, it is recognized that the majority of patients with cancer and hypercalcemia have humoral hypercalcemia, as determined by elevated urinary cyclic AMP excretion.