For 2 weeks, a 58-year-old woman has experienced increasingfatigue with activity. She has needed to nap duringthe day, has not been able to perform her usual activities,and has missed 3 days of work. She also complains of“muscle aches”-mainly in her back. She denies headache,dyspnea, fever, hot or cold intolerance, and alteredmentation.
For 2 weeks, a 58-year-old woman has experienced increasingfatigue with activity. She has needed to nap duringthe day, has not been able to perform her usual activities,and has missed 3 days of work. She also complains of"muscle aches"--mainly in her back. She denies headache,dyspnea, fever, hot or cold intolerance, and alteredmentation.HISTORY
The patient had stage IIB (T2, N1, M0) cancer inthe left breast, which was treated 2 years ago with lumpectomy,axillary node dissection, postoperative chemotherapy(with doxorubicin and cyclophosphamide), andradiation. She is currently taking tamoxifen. Her most recentmammogram, obtained 2 months earlier, was normalexcept for postoperative changes in the left breast.PHYSICAL EXAMINATION
This woman appears fatigued but is in no acute distress.Temperature is 36.9oC (98.4oF); heart rate, 90 beatsper minute; respiration rate, 16 breaths per minute; andblood pressure, 134/68 mm Hg. No jugular-venous distention,bruits, or transmitted murmurs are noted in theneck. Chest is clear. Examination of the heart reveals normalS1 and S2 and no extra heart sounds or significantmurmurs. The left breast has a well-healed lumpectomyscar and no masses; there is no axillary adenopathy onthat side. There are no suspicious masses in the rightbreast and no right axillary adenopathy. Results of the remainderof the lymph node examination are unremarkable.Abdomen is soft and nontender, without organomegaly.No peripheral edema is noted. Cranial nerves areintact; no focal deficits are found.LABORATORY RESULTS
White blood cell count is 4600/μL, with normal differential;platelet count, 142,000/μL; hemoglobin level,11.2 g/dL; and hematocrit, 33.4 mL/dL. Thyroid-stimulatinghormone (TSH) level is 1.2 μIU/mL.RESULTS OF 2-WEEK FOLLOW-UP
Over the ensuing 2 weeks, mild nausea and anorexiadevelop, and the patient's oral intake decreases. Duringthe 3 days before her follow-up visit, she does not moveher bowels. She denies abdominal pain and dysuria buthas noticed nocturia and polyuria. Bowel sounds are mildlydiminished, but the abdomen is otherwise normal.Mucous membranes appear dry. Urinalysis reveals 2 to 3white blood cells per high-power field.What is the most appropriate next step for this patient?A. Obtain a flow cytometry analysis of her blood to evaluate for leukemia.B. Obtain an echocardiogram.C. Obtain a full chemistry panel.D. Prescribe a trial of antibiotics for presumed urinary tract infection (UTI).E. Obtain a CT or MRI scan of the brain.CORRECT ANSWER: CThis patient's persistent GI symptoms, as well as her fatigue,suggest a metabolic disorder, such as hypercalcemia.This patient's persistent GI symptoms, as well as her fatigue,suggest a metabolic disorder, such as hypercalcemia.This common metabolic complication of malignancyoccurs in 10% to 20% of patients with cancer. Breastcancer is second only to lung cancer as a cause of hypercalcemiaof malignancy and accounts for 25% of cases.1Hypercalcemia results from increased mobilizationof calcium from bone and increased renal tubular calciumreabsorption. Because the symptoms and signs associatedwith its development are nonspecific, diagnosis is frequentlydelayed. However, complaints such as fatigue andGI symptoms(nausea andvomiting, anorexia,constipation)--althoughnonspecific--occur in nearlyall patients andcan be earlyclues.2 Polyuriais also commonin hypercalcemia,becausethe ability of thekidneys to concentrateurine isimpaired.Although acomplete bloodcell count andmeasurement of TSH level were reasonable studies withwhich to begin the workup (they are indicated in theworkup of all patients who complain of fatigue), to determinewhether a metabolic disorder is present, a full chemistrypanel is needed. Thus, choice C is the most appropriatenext step.Although hypercalcemia can occur in persons withoutovert metastatic disease--via the mechanism of humoralhypercalcemia of malignancy--hypercalcemia in acancer patient mandates a search for bone involvement.Moreover, this patient has had persistent musculoskeletalpain. This symptom suggests bony metastasis as a unifyingmechanism underlying the entire clinical picture.Brain imaging (choice E) is not indicated in patientswho have no neurologic signs or symptoms. Because theurinalysis results are relatively normal, a UTI is unlikelyand therefore choice D is incorrect.Although patients who receive an anthracycline havea 0.5% to 1% increased risk of cardiomyopathy, this patienthas displayed no signs or symptoms of the disorder; thus,an echocardiogram (choice B) is not warranted. Fatigueof recent onset should not be ascribed to chemotherapyand radiation given 2 years earlier. Also, patients who receivedanthracycline and alkylating chemotherapy are atlow risk (0.2% to 1%) for secondary myelodysplastic syndromeor leukemia. These late complications of breastcancer chemotherapy are not likely here.3 Moreover, thiswoman's complete blood cell count and normal differentialmake this last rare complication even less likely.Thus, a flow cytometry study (choice A) is not the optimalnext step.Treatment of hypercalcemia of malignancy. Mosthypercalcemic patients present in a volume-contractedstate as a result of decreased oral intake and polyuriacaused by renal tubular dysfunction. Initial therapy consistsof the infusion of normal saline. The addition of a diureticafter hydration is not likely to provide further benefit,and diuresis is clearly inappropriate as the sole therapy.Hydration alone does not produce a complete responsein most patients with hypercalcemia of malignancy;additional therapy is required. The majority of thesepatients are treated with bisphosphonates, administered at3- to 4-week intervals. Bisphosphonates inhibit osteoclasticactivity and have also been associated with a reductionin fractures and other skeletal events in patients withbreast cancer and bone metastasis.4Outcome of this case. A chemistry panel was obtained,which revealed the following values: sodium, 148mEq/L; chloride, 110 mEq/L; potassium, 3.6 mEq/L; bicarbonate,28 mEq/L; blood urea nitrogen, 34 mg/dL;creatinine, 2 mg/dL; calcium, 12.4 mg/dL; and albumin,3.7 g/dL. Hypercalcemia of malignancy was diagnosed.The patient was given saline infusions and bisphosphonatetherapy. By the third day, her calcium level wasnormal. Whole-body bone scanning and MRI revealedmetastatic disease in vertebrae T5, T8, and L2 through L4,and in the left ribs and sacrum.This case highlights the need to remain vigilant forsigns and symptoms of recurrent disease in patients whohave a history of breast cancer. Recurrences have beenreported up to 20 years after an initial diagnosis.
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