Veterinary Medicine - March 2008 - (Page 153)

Other nonspeci c clinical signs associated with glucagonomas in dogs include normocytic normochromic nonregenerative anemia and weight loss.2 When present, anemia can be explained by the suppression of bone marrow erythropoiesis (i.e. anemia of chronic disease) induced by the neoplasm, and the weight loss is a result of glucagon’s catabolic effects.4 they should be considered as a differential diagnosis in any patient exhibiting clinical and histologic changes consistent with super cial necrolytic dermatitis. A diagnosis of glucagonoma should be based on elevated plasma glucagon concentrations and a con rmed neuroendocrine pancreatic tumor. In addition, Kurt L. Zimmerman, DVM, PhD Department of Biomedical Sciences & Pathobiology Virginia-Maryland Regional College of Veterinary Medicine Virginia Tech Blacksburg, VA 24061 Shawn P. Clark, DVM, PhD, DACVP Bristol-Myers Squibb 2400 W. Lloyd Expressway Evansville, IN 47721 Kate Hill, BVSc(Hons), DACVIM Veterinary Teaching Hospital Massey University Palmerston North, New Zealand Peter Laverty, BVSc, MACVSc, DACVS Melbourne Veterinary Specialist Centre 70 Blackburn Road Glen Waverley, VIC 3150 Australia Armando Irizarry, DVM, PhD, DACVP Eli Lilly & CO 2001 W. Main St. Greenﬁeld, IN 46140 Tanya LeRoith, DVM, PhD, DACVP Department of Biomedical Sciences & Pathobiology Virginia-Maryland Regional College of Veterinary Medicine Virginia Tech Blacksburg, VA 24061 Dennis DeNicola, DVM, PhD, DACVP IDEXX Laboratories 1 IDEXX Drive Westbrook, ME 04092 Elevated serum glucagon concentration The hallmark laboratory nding in people with glucagonomas is elevated fasting serum glucagon concentrations. High metastatic rates are also commonly associated with glucagonomas in people.2 As in this case report, glucagon concentrations were markedly elevated in seven of nine previously reported cases in dogs.5,8 A pancreatic mass was identi ed in seven of the nine canine glucagonoma cases; however, in two dogs, a primary pancreatic tumor was not identi ed. The diagnosis of glucagonoma in those two dogs was reached by demonstrating glucagon immunoreactivity in hepatic metastases.5,10 Metastases were identi ed in ve of the nine cases, most frequently involving the liver and the mesenteric or hepatic lymph nodes. In this dog, at the time of euthanasia, no metastatic disease was found despite the plasma glucagon concentration’s being above the published canine reference interval, suggesting local or metastatic tumor growth. Similar to this case and to cases in people, all previously reported cases of canine glucagonoma were immunoreactive for glucagon, either singly or in combination with insulin, somatostatin, islet amyloid pancreatic polypeptide, or pancreatic polypeptide. This nding underscores the importance of plasma glucagon concentrations in reaching a de nitive diagnosis of glucagonoma and glucagonoma-associated paraneoplastic skin disease. the characteristic cutaneous changes are strongly suggestive of the disease. Immunohistochemical analysis of tumor tissue is a helpful diagnostic tool; however, it is limited by the ability of many islet cell tumors to produce multiple hormones. Thus, plasma glucagon concentrations are necessary for a de nitive diagnosis. As demonstrated by this case and from previous reports, the prognosis for patients with and without surgical excision of their neoplasm remains poor to guarded. REFERENCES 1. Sherwin RS, Hendler R, DeFronzo R, et al. Glucose homeostasis during prolonged suppression of glucagon and insulin secretion by somatostatin. Proc Natl Acad Sci USA 1997;74:348-352. 2. Chastain MA. The glucagonoma syndrome: a review of its features and discussion of new perspective. Am J Med Sci 2001;321:306-320. 3. Bloom SR, Polak JM. Glucagonoma syndrome. Am J Med 1987;82(5B):25-36. 4. Wermers RA, Fatourechi V, Wynne AG, et al. The glucagonoma syndrome. Clinical and pathologic features in 21 patients. Medicine (Baltimore) 1996;75:53-63. 5. Allenspach K, Arnold P, Glaus T, et al. Glucagon-producing neuroendocrine tumour associated with hypoaminoacidaemia and skin lesions. J Small Anim Pract 2000;41:402-406. 6. Turek MM. Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature. Vet Dermatol 2003;14:279-296. 7. Capen C. Tumors of the endocrine gland. In: Moulton J, ed. Tumors in domestic animals. 3rd ed. Berkeley, Calif: University of California Press, 1990;616-623. 8. Cerundolo R, McEvoy F, McNeil PE, et al. Ultrasonographic detection of a pancreatic glucagon-secreting multihormonal islet cell tumour in a dachshund with metabolic epidermal necrosis. Vet Rec 1999;145:662-666. 9. Gross TL, O’Brien TD, Davies AP, et al. Glucagon-producing pancreatic endocrine tumors in two dogs with super cial necrolytic dermatitis. J Am Vet Med Assoc 1990;197:1619-1622. 10. Miller WH, Anderson WI, McCann JP. Necrolytic migratory erythema in a dog with a glucagon-secreting endocrine tumor. Vet Dermatol 1991;2:179-182. 11. Torres S, Johnson K, McKeever P, et al. Super cial necrolytic dermatitis and a pancreatic endocrine tumour in a dog. J Small Anim Pract 1997;38:246-250. 12. Hawkins KL, Summers BA, Kuhajda FP, et al. Immunocytochemistry of normal pancreatic islets and spontaneous islet cell tumors in dogs. Vet Pathol 1987;24:170-179. 13. O’Brien TD, Hayden DW, O’Leary TP, et al. Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid. Vet Pathol 1987;24:308-314. 14. Torres SM, Caywood DD, O’Brien TD, et al. Resolution of super cial necrolytic dermatitis following excision of a glucagon-secreting pancreatic neoplasm in a dog. J Am Anim Hosp Assoc 1997;33:313-319. 15. Byrne KP. Metabolic epidermal necrosis-hepatocutaneous syndrome. Vet Clin North Am Small Anim Pract 1999;29:1337-1355. EXTRAS See for information on pancreatic neoplasia in dogs. CONCLUSION Although glucagonomas are uncommon tumors in veterinary medicine, VETERINARY MEDICINE March 2008 153 http://www.vetstreamcanis.com/ACI/March08/VMD1/dis02121.asp

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Veterinary Medicine - March 2008

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