Oncologic emergencies for the internist - Cleveland Clinic Journal of ...
Oncologic emergencies for the internist - Cleveland Clinic Journal of ... 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
Not available for online publication.See print version of theCleveland Clinic Journal of Medicine25-vitamin D to 1,25-vitamin D appears to beresponsible for some of the hypercalcemia ofmalignancy seen in both Hodgkin lymphomaand non-Hodgkin lymphoma. 14,15 Thus, it issimilar to the hypercalcemia associated withsarcoidosis and other granulomatous diseases.Direct tumor invasion into bony structures.Individual tumor cells secrete a varietyof mediators, including interleukin-1, interleukin-6,and tumor necrosis factor, that upregulatelocal osteoclastic activity, causingcalcium to be released into the serum. 16Treatment of hypercalcemia of malignancyTreatment must address these various mechanismsto be effective; ideally, the best way is byreducing or eliminating the causative malignancy.Hydration. Patients with hypercalcemiaof malignancy invariably present with somedehydration caused by calcium’s effect on thekidney. Thus, appropriate managementshould begin with giving intravenous fluids toimprove symptoms and to induce excretion ofcalcium. However, even with adequatehydration, most patients do not achieve anacceptable calcium level, and thus additionaltherapies are used to control the renal andskeletal mechanisms of hypercalcemia ofmalignancy.Diuresis with furosemide increases renalexcretion of calcium, but should be startedonly when the patient has been adequatelyhydrated—otherwise it will exacerbate thefree water loss relative to the loss of sodiumand calcium.Bisphosphonates. Most experts recommendusing bisphosphonates, most oftenpamidronate, to produce a sustained decreasein the calcium level by inhibiting osteoclasticactivity and calcium resorption from bone. 17Pamidronate is given intravenously in either aHypercalcemicpatientsinvariably aredehydratedCLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 3 MARCH 2002 213
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Not available <strong>for</strong> online publication.See print version <strong>of</strong> <strong>the</strong><strong>Cleveland</strong> <strong>Clinic</strong> <strong>Journal</strong> <strong>of</strong> Medicine25-vitamin D to 1,25-vitamin D appears to beresponsible <strong>for</strong> some <strong>of</strong> <strong>the</strong> hypercalcemia <strong>of</strong>malignancy seen in both Hodgkin lymphomaand non-Hodgkin lymphoma. 14,15 Thus, it issimilar to <strong>the</strong> hypercalcemia associated withsarcoidosis and o<strong>the</strong>r granulomatous diseases.Direct tumor invasion into bony structures.Individual tumor cells secrete a variety<strong>of</strong> mediators, including interleukin-1, interleukin-6,and tumor necrosis factor, that upregulatelocal osteoclastic activity, causingcalcium to be released into <strong>the</strong> serum. 16Treatment <strong>of</strong> hypercalcemia <strong>of</strong> malignancyTreatment must address <strong>the</strong>se various mechanismsto be effective; ideally, <strong>the</strong> best way is byreducing or eliminating <strong>the</strong> causative malignancy.Hydration. Patients with hypercalcemia<strong>of</strong> malignancy invariably present with somedehydration caused by calcium’s effect on <strong>the</strong>kidney. Thus, appropriate managementshould begin with giving intravenous fluids toimprove symptoms and to induce excretion <strong>of</strong>calcium. However, even with adequatehydration, most patients do not achieve anacceptable calcium level, and thus additional<strong>the</strong>rapies are used to control <strong>the</strong> renal andskeletal mechanisms <strong>of</strong> hypercalcemia <strong>of</strong>malignancy.Diuresis with furosemide increases renalexcretion <strong>of</strong> calcium, but should be startedonly when <strong>the</strong> patient has been adequatelyhydrated—o<strong>the</strong>rwise it will exacerbate <strong>the</strong>free water loss relative to <strong>the</strong> loss <strong>of</strong> sodiumand calcium.Bisphosphonates. Most experts recommendusing bisphosphonates, most <strong>of</strong>tenpamidronate, to produce a sustained decreasein <strong>the</strong> calcium level by inhibiting osteoclasticactivity and calcium resorption from bone. 17Pamidronate is given intravenously in ei<strong>the</strong>r aHypercalcemicpatientsinvariably aredehydratedCLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 69 • NUMBER 3 MARCH 2002 213
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