Hypercalcemia in Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review

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Abstract

Objective . We here report a patient with upper urinary tract urothelial carcinoma with hypercalcemia likely due to elevated 1,25-dihydroxyvitamin D. Methods . We present a clinical case and a summary of literature search. Results . A 57-year-old man, recently diagnosed with a left renal mass, for which a core biopsy showed renal cell carcinoma, was admitted for hypercalcemia of 11.0 mg/mL He also had five small right lung nodules with a negative bone scan. Both intact parathyroid hormone and parathyroid hormone-related peptide were appropriately low, and 1,25-dihydroxyvitamin D was elevated at 118 pg/dL. The patient’s calcium was normalized after hydration, and he underwent radical nephrectomy. On the postoperative day 6, a repeat 1,25-dihydroxyvitamin D was 24 pg/mL with a calcium of 8.1 mg/dL. Pathology showed a 6 cm high-grade urothelial carcinoma with divergent differentiation. We identified a total of 27 previously reported cases with hypercalcemia and upper tract urothelial carcinoma in English. No cases have a documented elevated 1,25-dihydroxyvitamin D level. Conclusion . This clinical course suggests that hypercalcemia in this case is from the patient’s tumor, which was likely producing 1,25-dihydroxyvitamin D. Considering the therapeutic implications, hypercalcemia in patients with upper urinary tract urothelial carcinoma should be evaluated with 1,25-dihydroxyvitamin D.

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Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma.

Ganesh Palapattu, Blaine Kristo, Jacob Rajfer (2002)

Renal cell carcinoma is unique among the genitourinary malignancies in that close to one third of affected patients show signs and symptoms of a paraneoplastic syndrome. The paraneoplastic syndromes associated with renal cell carcinoma range from those manifesting in constitutional symptoms (ie, fever, cachexia, and weight loss) to those that result in specific metabolic and biochemical abnormalities (ie, hypercalcemia, nonmetastatic hepatic dysfunction, amyloidosis, etc). The presence of a paraneoplastic syndrome in a patient with renal cell carcinoma is neither a marker of metastatic disease nor necessarily indicative of a poor prognosis. The importance of understanding the pathophysiology and biology behind the many paraneoplastic syndromes associated with renal cell carcinoma lies in the fact that the presence of these protean symptoms may be the initial presentation of either primary or recurrent disease. In this review, we will describe the proposed mechanisms of action of the many paraneoplastic syndromes associated with renal cell carcinoma as well as outline the clinical evaluation and treatment options currently available for these noteworthy disorders.

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Extrarenal Expression of 25-Hydroxyvitamin D3-1 -Hydroxylase

D. Zehnder (2001)

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Clinical review: Rare causes of hypercalcemia.

John Bilezikian, Howard Jacobs (2005)

Although hypercalcemia is usually caused by primary hyperparathyroidism or malignancy, a number of other conditions can be important to consider. This review considers unusual causes of hypercalcemia that are generally not found in reviews on this subject. Articles describing rarely reported associations between hypercalcemia and unusual causes were identified through a computer search of the terms hypercalcemia/etiology and through the references listed in those articles. We grouped the 58 different reports into categories defined by a presumed etiology: increased levels of 1,25-dihydroxyvitamin D or PTHrP, occult milk-alkali syndrome, and undefined mechanisms. Reports in infants and children are listed separately, as are reports of pseudohypercalcemia, situations that are not truly hypercalcemic because the ionized calcium is normal. In some situations, as this review points out, a number of unusual causes of hypercalcemia are important to consider. The search for an elusive cause of hypercalcemia is best accomplished by the most likely potential mechanism. An orderly search in this manner is likely to reveal the underlying cause. That so many patients have been described with rare and usually poorly understood causes of hypercalcemia highlights our incomplete understanding of calcium metabolism in humans and suggests additional areas in which directed clinical investigation might improve our knowledge of the normal metabolism of calcium.