MEDizzy - A 68-year-old woman with stage IIIB squamous cell carcinoma

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Combined Endocrinology II

A 68-year-old woman with stage IIIB squamous cell carcinoma of the lung is admitted to the hospital because of altered mental status and dehydration. Upon admission, she is found to have a calcium level of 19.6 mg/dL and phosphate of 1.8 mg/dL. Concomitant measurement of parathyroid hormone was 0.1 pg/mL (normal 10–65 pg/mL), and a screen for parathyroid hormone–related peptide was positive. Over the first 24 h, the patient receives 4 L of normal saline with furosemide diuresis. The next morning, the patient’s calcium is now 17.6 mg/dL and phosphate is 2.2 mg/dL. She continues to have delirium. What is the best approach for ongoing treatment of this patient’s hypercalcemia?

ExplanationMalignancy can cause hypercalcemia by several different mechanisms, including metastasis to bone, cytokine stimulation of bone turnover, and production of a protein structurally similar to parathyroid hormone by the tumor. This protein is called parathyroid hormone–related peptide (PTHrp) and acts at the same receptors as parathyroid hormone (PTH). Squamous cell carcinoma of the lung is the most common tumor associated with the production of PTHrp. Serum calcium levels can become quite high in malignancy because of unregulated production of PTHrp that is outside of the negative feedback control that normally results in the setting of hypercalcemia. PTH hormone levels should be quite low or undetectable in this setting. When hypercalcemia is severe (>15 mg/ dL), symptoms frequently include dehydration and altered mental status. The electrocardiogram may show a shortened QTc interval. Initial therapy includes large-volume fluid administration to reverse the dehydration that results from hypercalciuria. In addition, furosemide is also added to promote further calciuria. If the calcium remains elevated, as in this patient, additional measures should be undertaken to decrease the serum calcium. Calcitonin has a rapid onset of action with a decrease in serum calcium seen within hours. However, tachyphylaxis develops, and the duration of benefit is limited. Pamidronate is a bisphosphonate that is useful for the hypercalcemia of malignancy. It decreases serum calcium by preventing bone resorption and release of calcium from the bone. After IV administration, the onset of action of pamidronate is 1–2 days with a duration of action of at least 2 weeks. Thus, in this patient with ongoing severe symptomatic hypercalcemia, addition of both calcitonin and pamidronate is the best treatment. The patient should continue to receive IV fluids and furosemide. The addition of a thiazide diuretic is contraindicated because thiazides cause increased calcium resorption in the kidney and would worsen hypercalcemia.