Oncologic emergencies for the internist - Cleveland Clinic Journal of ...

ONCOLOGIC EMERGENCIESKRIMSKY AND COLLEAGUESHyperkalemia isthe most lifethreateningproblem intumor lysissyndromeNot available foronline publication.See print version of theCleveland Clinic Journalof MedicineFeatures of tumor lysis syndromeHyperuricemia. Catabolism of largeamounts of both RNA and DNA causes uricacid levels to rise fairly quickly. Normally, uricacid remains in the ionized state in the body;however, increased levels can lead to urateprecipitation in the distal tubule. 3 The resultof precipitation is an overall decrease in renalfunction.Hyperphosphatemia and hypocalcemiaalso result from the above process. Phosphatelevels in neoplastic cells can be as much as fourtimes higher than in normal cells. 4,5 Thebreakdown and release of phosphate is initiallycompensated for by increased renal excretion.However, as the concentration of phosphateincreases, it combines with calcium and precipitatesin the renal tubule as well as in thesoft tissues. Consequently, hypocalcemia andrenal failure develop. 6 Clinically, hypocalcemiacan manifest as agitation, tetany, andbone pain.Hyperkalemia is perhaps the most lifethreateningderangement in tumor lysis syndrome.The sudden increase in potassiumresults in the well-defined clinical presentationof cardiac arrhythmias and death.All the above metabolic derangements aremade worse by preexisting renal insufficiency.Treatment of tumor lysis syndromeProphylaxis is the first step in treatment (TABLE2). 7 If a patient is found to be at high risk fortumor lysis syndrome, he or she shouldpromptly be started on both intravenous fluidand allopurinol if there is no contraindicationto it. Close observation during therapy is alsoessential, as transient, urgent hemodialysismay reverse the toxicity.■ HYPERCALCEMIA OF MALIGNANCYHypercalcemia of malignancy occurs inapproximately 10% to 20% of cancerpatients, 8,9 most often with lung cancer,breast cancer, and the hematologic malignanciessuch as multiple myeloma and lymphoma.10Features of hypercalcemia of malignancySymptoms vary depending on the degree ofhypercalcemia and how quickly it develops.Acute symptoms include nausea, vomiting,constipation, polyuria, polydipsia, muscleweakness, acute renal insufficiency, and mentalstatus changes. Chronic symptoms includekidney stones, bone pain, and depression.Mechanisms of hypercalcemiaof malignancyNormally, calcium levels are maintained bythe interaction of parathyroid hormone, calcitonin,and 1,25(OH) 2 -vitamin D. The disordersof calcium metabolism in malignancyusually represent an alteration in one of thesepathways or extensive lytic bone lesions.Parathyroid hormone-related peptide.The most common cause of hypercalcemia ofmalignancy, classically seen in squamous celllung cancer, is a syndrome mediated by productionof a parathyroid hormone-related peptide(PTHrP). Structurally similar to PTH atthe amino acid terminus, PTHrP binds toparathyroid hormone receptors, mobilizes calciumfrom bones, and increases renal reabsorptionof calcium. Evidence suggests thatthere might be some clinical utility to measuringPTHrP because significant elevations ofPTHrP seem to correlate with poorer outcomes.11–13Abnormal production of calcitriol (1,25-vitamin D). The deregulated conversion of210 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 3 MARCH 2002