Document 2NQdVyMgYed6Nz8amxw9nOrpp

CASE REPORTS Refer to: Orr LE: Fanconi syndrome and oat cell carcinoma of the lung. West J Med 133:250-251, Sep 1980 Fanconi Syndrome and Oat Cell Carcinoma of the Lung LEO E. ORR, MD Los Angeles The renal tubular dysfunction associated with Fanconi syndrome* is characterized by the renal wasting of circulating electrolytes, glucose and amino acids in the presence of metabolic acidosis and minimal azotemia.12 In addition to the genetic causes of this malady, various acquired disorders have been identified, principally results of renal toxicity from heavy metals and orally ingested drugs, and from the disorders associated with paraproteinemias.3'4 This report presents an instance in which Fan coni syndrome has been related to oat cell car cinoma of the lung. Report of a Case A 56-year-old black woman, a domestic worker, was well until May 1976. However, pro gressively increasing weakness, diffuse body aches The Western Journal's style regarding eponyms is that they are not written in the possessive form; therefore Graves disease, Ewing sarcoma and Paget disease. A explanation may be found on page 78 of the July 1978 issue. From the Medical Oncology Section, Southern California Cancer Center, California Hospital Medical Center, Los Angeles. Submitted, revised, November 15, 1979. Reprint requests to: Leo E. Orr, MD, Medical Oncology Sec tion, Southern California Cancer Center, California Hospital Medical Center, 1414 S. Hope St., Los Angeles, CA 90015. and nausea developed and she was admitted to hospital in June. On physical examination the patient appeared chronically ill and was able to stand only with assistance. Blood pressure was 115/65 mm of mercury with the patient sitting. There was evi dence of mild muscle wasting along the temporal regions, the pectoral region and the proximal mus culature of the legs. Other findings of the examina tion were normal. A routine x-ray study of the chest showed a left upper lobe infiltrate. The hemoglobin value was 13.2 grams per dl, the leukocyte count was 3,500 with 42 percent neutrophils and the platelet count was 98,000 per cu mm. The results of blood chemistry studies and analyses of urine are sum marized in Tables 1 and 2. Bronchoscopy with biopsy showed the presence of oat cell carcinoma. Findings on brain, liver and bone scans were nor mal. A bone marrow biopsy disclosed infiltration with oat cell carcinoma. Electrolyte abnormalities and abnormal results on analysis of urine were noted in the initial laboratory studies, but the causes of these findings were not aggressively pur sued. The patient was treated with cyclophospha mide, vincristine and methotrexate. She rapidly regained her strength and normal habitus. A com plete remission was achieved approximately nine weeks after diagnosis. The patient was readmitted to hospital in June 1977 because of weakness, lethargy, tremors, an orexia and general malaise. Examination disclosed pronounced weakness of the musculature and a diffuse tremor. No abnormalities were seen on an x-ray film of the chest and a liver scan. A bone scan showed increased vertebral uptake. Blood TABLE 1.--Results of Blood Chemistry Studies in Patient With Oat Cell Lung Carcinoma and Renal Tubular Dysfunction June 1976 June 1977 October November 1977 1977 Body surface area (sq m) ...................... ........ Plasma urate (mg/dl) ............................ ........ Plasma glucose (mg/dl) ........................ ........ Serum cholesterol (mg/dl) .................... ........ Blood urea nitrogen (mg/dl) .............. ........ Creatinine (mg/dl) ................................. ........ Serum phosphorus (mg/dl) .................. ........ Serum calcium (mg/dl) ........................ ........ Serum albumin (grams/dl) .................... ........ Serum sodium (mEq/liter) .................... ........ Serum potassium (mEq/liter) .............. ........ Serum carbon dioxide (mEq/liter) ----- ........ Serum chloride (mEq/liter) .................. ........ 1.87 2.8 76.0 258.0 13.0 0.7 2.2 9.4 3.7 132.0 3.1 19.0 112.0 1.6 54.0 221.0 11.0 0.6 1.1 8.7 3.5 128.0 2.1 17.0 106.0 ... 1.7 45.0 218.0 20.0 0.6 1.9 8.8 3.3 112.0 2.1 18.0 98.0 4.7 86.0 254.0 11.0 1.0 3.4 9.4 3.8 141.0 4.4 25.0 102.0 250 SEPTEMBER 1980 133 3 CASE REPORTS TABLE 2.--Results of Analyses of Urine in Patient With Oat Cell Lung Carcinoma and Renal Tubular Dysfunction June 1976 June 1977 October November 1977 1977 24-hour glucose (mg) ................ ........................ Clinitest ................................................................. . Ketone .................................................................... . Protein ................................................................... . Tm phosphorus (% filtered load) ....................... Amino acids (grams/24 hours) ......................... 24-hour urinary sodium/potassium (mEq/liter) . . Urinary urate (mg/24 hours) ........................... Tm PAH (mg/mm) ............................................. Cin (ml/mm) ....................................................... Cpah (ml/mm) ..................................................... i+ 1+ 1+ 116/88 570 3+ 1+ 1+ 2.2 88/96 622 88 121 605 512 3+ 2+ 1+ 32% 2.6 113/108 560 85 106 581 Cin-insulin clearance Cpah = para-aminohippurate clearance PAH = para-aminohippuric acid Tm = maximal tubular excretory capacity 224 1+ 0 0 61% 1.4 90/46 324 77 113 560 chemistry studies disclosed a metabolic acidosis with hyponatremia, hypokalemia, hypophosphate mia and a subnormal uric acid titer. Analysis of urine showed glycosuria, proteinuria and amino aciduria. Renal evaluation disclosed the presence of normal glomerular and tubular secretory func tion, although the quantities of sodium, potassium, uric acid, amino acids and glucose delivered through the urine were abnormally high. The pa tient was given therapy with citrate of potassium and potassium phosphate. Chemotherapy was al tered to include doxorubicin and ccnu (chloroethyl cyclohexyl nitrosourea [lomustine]). Serum chem istry values improved although the urinary abnor malities persisted. The tremors and weakness sub sided. Another admission was necessitated in October 1977, heralded by diffuse muscle aches, severe weakness, headaches, cervical spinal pain and dyspnea. An x-ray study of the chest showed a mass in the left lung extending into the media stinum. A bone scan indicated progression of os seous disease. Laboratory data mirrored those present in October 1977. Serum immunoelectro phoresis was normal. Urine immunoelectrophore sis showed no abnormal gammaglobulins. A study of urine for heavy metals showed no abnormal levels. Rheumatoid factor, latex fixation titer, lupus erythematosus preparation, cold agglutinins and C3 complement titer were normal. Additional chemotherapy was instituted with vinblastine, pro carbazine and megadoses of methotrexate with folinic acid rescue. A partial remission was ob tained with resolution of the pulmonary mass, lessening of bone pain, and decrease of weakness and tremors. The electrolyte abnormalities again improved when potassium citrate and potassium phosphate were given. The improved status con tinued until January 1978 when Gram-negative septicemia occurred during a period of pancyto penia and the patient died. Discussion It is uncertain whether the patient had renal tubular dysfunction antedating the occurrence of the oat cell carcinoma. However, the absence of previous symptoms, the initially normal findings on roentgenograms and the patient's initially nor mal habitus was inconsistent with chronic Fanconi syndrome.1 An autopsy was not permitted, and therefore the presence or absence of an anatomic defect can only be theorized. However, it is pos sible that the cause of the renal tubular dysfunc tion was the presence of an unidentified toxin, probably produced by the neoplasm, being de posited in the renal tubular parenchyma and af fecting normal reabsorptive mechanisms. Our studies of the immediate family of this patient were limited to serum electrolyte studies and analyses of urine; however, these persons are in good health and laboratory studies show no ab normalities. Summary A case of a patient with oat cell carcinoma of the lung and concomitant Fanconi syndrome is presented. Evidence suggests that the renal tubu lar dysfunction was acquired and became sympto matic during the presence of the neoplasm. REFERENCES 1. Milne MD: Renal tubular dysfunction, chap 2, In Strauss MB, Welt LG (Eds): Diseases of the Kidney, vol 2, 2nd Ed. Boston, Little, Brown and Co, 1971, pp 1094, 1095 2. Sirota JH, Hamerman D: Renal function studies in an adult with the Fanconi syndrome. Am J Med 19:138-152, Jan 1954 3. Wallis LA, Engle RL: The adult Fanconi syndrome. Am J Med 25:13-23, Jan 1957 4. Weinstein B, Irreverre F, Watkin DM: Lung carcinoma, hypouricemia and aminoaciduria. Am J Med 39:520-526, Sep 1965 THE WESTERN JOURNAL OF MEDICINE 251