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Hypercalcemia of Malignancy with Simultaneous Elevation in Serum Parathyroid Hormone-Related Peptide and 1,25-Dihydroxyvitamin D in a Patient with Metastatic Renal Cell Carcinoma
Institution:1. Department of Internal Medicine, and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.;2. Department of Pathology, and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.;3. Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas.;1. Department of Physiology, University of Tübingen, Tübingen, Germany;2. Department of Molecular Pathology, University of Tübingen, Tübingen, Germany;3. Department of Nephropathology, University Hospital Erlangen, Erlangen, Germany;4. Proteome Center, University of Tübingen, Tübingen, Germany;5. Novartis Oncology, Novartis International AG, Hyderabad, India;6. Department of Radiology, University of Tübingen, Tübingen, Germany
Abstract:ObjectiveTo determine the cause of refractory hypercalcemia in a patient with metastatic renal cell carcinoma.MethodsWe describe the clinical, pathologic, and immunostain findings in a patient with metastatic renal cell carcinoma and hypercalcemia of malignancy refractory to intravenous bisphosphonates.ResultsA 57-year-old man with a remote history of clear cell renal cell carcinoma was referred to our clinic for evaluation of resistant hypercalcemia 12 years after nephrectomy. The patient had simultaneous elevation of serum 1,25-dihydroxyvitamin D and parathyroid hormone-related peptide. Computed tomographic scan of the chest and abdomen demonstrated numerous ring-enhancing lesions in the liver, and histologic examination of a biopsy specimen revealed liver tissue infiltrated by a malignant neoplasm composed of cells with clear and eosinophilic cytoplasm, arranged in tubules and nests. Findings were morphologically consistent with renal cell carcinoma of clear cell type, and positive immunostaining with the epithelial markers EMA and CAM 5.2 were supportive of the morphologic impression of renal cell carcinoma. The tumor showed expression of 25-hydroxyvitamin D 1a-hydroxylase by immunostaining. After failing to respond to intravenous bisphosphonates, the hypercalcemia improved with prednisone treatment.ConclusionsIn some patients with renal cell carcinoma, hypercalcemia of malignancy is associated with simultaneous elevation in serum 1,25-dihydroxyvitamin D and parathyroid hormone-related peptide. As our case exemplifies, it is imperative to identify such patients because hypercalcemia due to elevated 1,25-dihydroxyvitamin D levels may respond better to glucocorticoid treatment than to the conventional bisphosphonate therapy. (Endocr Pract. 2009;15:234-239)
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