Acute pyelonephritis with anaplastic thyroid carcinoma producing granulocyte colony-stimulating factor
A 75-year-old woman presented with fever and loss of appetite. She had been treated for diabetes and hypertension for the past 20 years. Four years previously, she had taken levothyroxine sodium (Synthroid) for hypothyroidism, the cause of which was unknown, for several months. As euthyroid state was maintained, she had been taken off medication for the past 3 years and was followed up for simple goiter. She was a non-smoker and had not previously drunk alcohol. Upon physical examination, her body temperature was 37.5℃, her pulse rate was 128 beats/min, and her blood pressure was 110/70 mmHg. She looked chronically ill but was alert. A tender fist-sized, warm, soft mass was observed in the hypochondriac region of the anterior surface of the neck. No specific abnormalities were noted on examination of the chest or abdomen, except for tenderness at the left costovertebral angle.\nLaboratory tests on peripheral blood revealed significant leukocytosis (34.9×109/L) with neutrophilia (91%). On peripheral blood smear, neutrophils had normal morphological features and immature cells were not detected. The hemoglobin level was 8.3 g/dL, and the platelet count was 547×109/L. Levels of acute phase reactants were elevated, with erythrocyte sedimentation rate (ESR) of 47 mm/hr and C-reactive protein (CRP) level of 221 mg/L. Other laboratory findings were as follows: blood urea nitrogen, 35.8 mg/dL; serum creatinine, 1.58 mg/dL; serum glucose, 437 mg/dL; total cholesterol, 89 mg/dL; serum sodium, 128 mEq/L; serum potassium, 4.4 mEq/L; serum chloride, 88 mEq/L; serum parathyroid hormone, 58.5 pg/mL; serum calcium, 9.5 mg/dL; and serum albumin, 3.5 g/dL. Urinalysis revealed pyuria (white blood cells [WBC] count >61/HPF).\nOn the basis of these results, APN was diagnosed. While treatment for APN was ongoing, the mass on the patient's neck was examined. Results of the thyroid function test were compatible with sick euthyroid syndrome, considering the patient's seriously ill condition: low T3 levels (16.8 ng/dL), normal T4 levels (8.0 µg/dL), slightly elevated free T4 levels (1.89 ng/dL), and suppressed thyroid stimulating hormone levels (0.02 µIU/mL). Tests for all anti-thyroid autoantibodies, including thyroid stimulating immunoglobulins, anti-thyroglobulin antibody, and anti-microsomal antibody, were negative. Chest radiography showed that both lungs had thyroid lesions with dense calcifications on both sides and multiple nodules. Computed tomography (CT) scan of the neck and chest showed a large thyroid mass and multiple metastatic nodules in both lung fields with cervical, supraclavicular, and mediastinal lymphadenopathy (). Fine needle aspiration of the thyroid mass was performed, and anaplastic thyroid carcinoma was diagnosed following cytological examination ().\nPyuria and fever were alleviated after administration of 400 mg/day ciprofloxacin for 3 days. On the fifth day of ciprofloxacin administration, treatment was switched to cefotaxime because ciprofloxacin-resistant Escherichia coli was detected in the patient's urine. After cefotaxime administration, bacterial growth was no longer detected in the urine (day 12 of hospital stay). However, the administration of antibiotics did not improve leukocytosis. The WBC count slightly decreased to 28.5×109/L by day 6 of hospital stay, but it steadily increased to 68.8×109/L by day 21 with 91% neutrophils. Although systemic symptoms related to infection improved, no significant increases in other inflammatory markers such as CRP were noted ().\nTo further investigate this persistent leukocytosis, the serum concentration of G-CSF was measured on day 21 of hospital stay, and it was found to be markedly increased at 1,010 pg/mL (normal range, 3.7-32.3 pg/mL; Quantikine ELISA Kit; R&D System, USA). Despite supportive care, the patient's condition rapidly deteriorated. Respiratory failure developed, and the patient died on day 23 of hospital stay.