JL203. Clinical Practice: Hypercalcemia of Malignancy
Steve Malangone, MSN, NP-C; Department of Hematology-Oncology, The University of Arizona Cancer Center, North Campus
Hypercalcemia is a common paraneoplastic syndrome associated with a variety of malignancies including lymphomas, aerodigestive, uterine, endometrial, breast, neuroendocrine, cervical, and renal cell carcinomas. The incidence of hypercalcemia in the cancer population is noted to be as high as 20-30%. Hypercalcemia associated with malignancy is associated with significant morbidity, including progressive cognitive dysfunction, dehydration, and acute renal failure. Sequelae of uncorrected hypercalcemia include dysrhythmia, coma, and death, with reports of as many as 50% mortality within 30 days of diagnosis. The advanced practitioner in oncology must be adequately prepared to identify and intervene appropriately in order to improve patient outcomes. The poster will present the clinical case of a patient with hypercalcemia (serum corrected calcium 14.2 mg/dL) in the setting of progression of well differentiated metastatic neuroendocrine tumor who presented with dehydration, progressive muscle weakness, lethargy, and confusion. The poster will describe clinical presentation, including laboratory values revealing elevated parathyroid-related hormone (PTHrP), symptoms including lethargy, confusion, and dehydration. Ultimately, the patient responded to aggressive hydration and diuresis, administration of intravenous bisphosphonates, and effective systemic management of disease. More broadly, the poster will include an overview of the presentation, etiology, therapeutic options, and practical considerations in managing this important oncologic syndrome. Diagnostic evaluation and consideration of differential diagnoses with an emphasis of various etiologies (osteolytic, humoral, increased calcitriol, and PTH secreting malignancies), general supportive measures, hydration, pharmacologic management, monitoring, and goals of therapy are included. The underlying pathophysiology of hypercaclemia of malignancy includes humoral, osteolytic, increased calcitriol, and parathyroid hormone (PTH) secreting malignancies. The most common mechanism (80%) is humoral hypercalcemia (HHM), in which tumor cells secrete ectopic PTHrP. In this disorder, PTHrP binds PTH receptors, inhibiting the action of osteoclasts and stimulating osteoblasts in the bone, and promoting renal tubular calcium reabsorption. Osteolytic hypercalcemia is directly related to the excessive release of calcium by osteoclasts in patients with osteolytic lesions. Increased calcitrol is related to increased conversion of inactive vitamin D to 1,25-dihydroxyvitamin D (calcitriol). This conversion, which is typically tightly regulated in the kidney through PTH and serum calcium concentration, occurs in an uninhibited fashion by way of PTH independent extrarenal malignant lymphocytes in the setting of lymphoma. Finally and rarely, PTH may be secreted, leading to hypercalcemia through the actions of PTH. Patients with mild hypercalcemia (serum calcium 10.5-12 mg/dL) can present with constipation, fatigue, and depression. Those with moderate hypercalcemia (12 to 14 mg/d) can develop polydipsia, polyuria, clinical dehydration, muscle weakness, and changes in mental status. Those with severe hypercalcemia can develop severe form of these symptoms. Diagnostic evaluation includes measurement of serum calcium, ionized calcium, PTH, and PTHrP. Patients with hypercalcemia of malignancy, secretion of endogenous parathyroid hormone (PTH) itself is suppressed by the PTHrP-mediated hypercalcemia. Goals of management include reduction in serum calcium, supportive management, and correction of underlying cause. The mainstay of therapy is hydration and calciuresis with IV normal saline and furosemide and intravenous bisphosphonate therapy. Ultimately, hypercalcemia is a clinical indication of progressive disease. Hypercalcemia of malignancy typically responds to control of systemic disease, and thus therapy to manage disease if available, should be initiated as soon as possible.
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