HYPERCALCEMIA 70A
A 71-year-old woman with lung cancer presents to her primary care provider with complaints of constipation, nausea, and increased urination. She also has new depression and generalized weakness. Her only medication is calcium carbonate, which she takes for prevention of osteoporosis. On cardiac examination, she has frequent ectopy. Her serum calcium level is elevated at 13.5 mg/dL, her serum parathyroid hormone (PTH) level is low, and her serum PTH-related protein (PTHrP) level is elevated.
What are the salient features of this patient’s problem? How do you think through her problem?
Salient features: Constipation, nausea, polyuria, weakness, depression, ectopy; known malignancy; elevated serum calcium; elevated serum PTHrP and low serum PTH levels
How to think through: Rapid diagnosis of hypercalcemia requires recognition of a constellation of symptoms. What are the broad categories of symptoms caused by hypercalcemia? (Gastrointestinal, e.g., constipation, nausea; neuropsychiatric, e.g., fatigue, weakness and altered mental status; renal, e.g., nephrolithiasis and polyuria; and cardiac, e.g., shortened QT interval and ectopy.) The cause of hypercalcemia is determined by a differential diagnosis with several key branch points; it is helpful to recall that most cases are caused by primary hyperparathyroidism or malignancy. The PTH was likely the first laboratory result in this case, with her low value ruling out hyperparathyroidism. From there, what causes were likely next considered? (Malignancy, granulomatous disease, hypervitaminosis D, milk-alkali syndrome, thyrotoxicosis.) Malignancy, the most common cause of hypercalcemia with a suppressed PTH level, is a concern here given the degree of serum calcium elevation. The elevated PTH-rP confirms this suspicion. What three cancer types most frequently cause hypercalcemia? (Breast and lung carcinoma and multiple myeloma.) How should she be managed in the short term? (She should be admitted to the hospital for an expedited diagnostic workup and therapy to lower her serum calcium level, including aggressive intravenous saline hydration and, when well hydrated, treatment with a bisphosphonate.)
HYPERCALCEMIA 70B
What are the essentials of diagnosis and general considerations regarding hypercalcemia?
Essentials of Diagnosis
Serum calcium level is 10.5 mg/dL; serum ionized calcium is 5.3 mg/dL.
Hypercalciuria usually precedes hypercalcemia.
Symptomatic and severe disease is often caused by malignancy; asymptomatic and mild disease is often caused by primary hyperparathyroidism.
General Considerations
Primary hyperparathyroidism and malignancy account for 90% of cases.
The hypercalcemia related to PTHrP production is the most common paraneoplastic endocrine syndrome.
Granulomatous diseases, such as sarcoidosis and tuberculosis, can cause hypercalcemia from production of active vitamin D3 (1,25 dihydroxyvitamin D3) by the granulomas.
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