Pancreatic Islet Cell Tumor Secreting Insulin‐Like Growth Factor Type‐II in a Dog

Abstract

7-year-old, intact female, Gordon Setter was examined for a 6-month history of progressive weakness and ataxia without loss of appetite or change in weight. The owner reported a slight improvement in the signs after food consumption. The dog was kept indoors, regularly vaccinated, and fed a commercial maintenance diet. Physical examination revealed weakness, difficulty in holding quadrupedal posture, and mild muscle hypotrophy. No abnormalities were detected in the CBC, morphologic evaluation of the smear, and coagulation profile. Biochemical profile showed moderate hypoglycemia on fasting (57 mg/dL; range 80–120 mg/dL). Abdominal ultrasound showed an hypoechoic pancreatic lesion of 23 mm in diameter, with indistinct margins and poorly contrasting with adjoining structures. Eco-guided fine needle biopsy of the lesion was performed. The cytologic specimen contained a large number of naked nuclei on a cytoplasmic background with indistinct margins, occasionally acinar structures with moderate anisokaryosis. The cytologic pattern, together with clinical signs, suggested neuroendocrine tumor. Abnormalities were not detected on chest X-ray in 3 standard projections. Serum concentration of insulin was 0.5 mIU/mL (range 4–16 mIU/mL). Serum concentration of insulin-like growth factor type II (IGF-II) was evaluated by immunoradiometric assay (IRMA) after chromatographic separation. Five hundred microliters of serum were obtained from the dog and gel-filtered by fast protein liquid chromatography on HyPrep Sephacryl S-200 High Resolution column (GE Healthcare, Amersham Place, Little Chalfont, Buckinghamshire, UK) in a buffer containing 50 mM NaH2PO4, 0.15 M NaCl, 0.02% NaN3 ,p H 7.2. Samples were eluted at 0.8 mL/min and collected at 3minute intervals. 1 The 44 fractions collected were pooled and tested for IGF-II immunoreactivity as follows: fractions 8–11 corresponding to the 150 kDa ternary complex, fractions 12–16 corresponding to the 45 kDa binary complex, and fractions 24–27 corresponding to the free form of IGF-II. The fraction of IGF-II bound to insulin-like growth factor binding protein (IGFBP)-3 and acid labile subunit (ALS) forming a 150-kDa complex was 0.8 ng/mL. Similarly to normal dogs, IGF-II was only measurable in the 150 kDa region and undetectable in the others. IGF-II was measured by IRMA with reagents kit provided by DSL, a on acid ethanol pretreated samples. 2 The sensitivity of the assay was 0.13 ng/mL; the intra-assay and interassay coefficients of variation were 5.3 and 8.7%, respectively. No detectable cross-reactivity was found against IGF-I, up to 480,000 ng/mL, proinsulin, up to 2mg/mL, and insulin, up to 4.3mg/mL.