Hypoglycaemic crisis induced by non-islet cell tumours in two dogs

https://doi.org/10.17221/145/2018-VETMEDCitation:Kim H., Kang J., Kang B., Yang M. (2019): Hypoglycaemic crisis induced by non-islet cell tumours in two dogs. Veterinarni Medicina, 64: 407-416.
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Two dogs were admitted for the diagnosis and treatment of neoplasia (a hepatic and a mammary tumour, respectively), lethargy, quadriparesis and abnormal mentation with hypoglycaemia. The blood analyses showed severe hypoglycaemia (1.32 and 1.60 mmol/l, respectively). Although prompt treatment, including intravenous administration of dextrose, was initiated, the blood glucose concentrations were not restored to a normal range. After the diagnostic procedures, no aetiology other than the hepatic tumour identified by the abdominal radiography and ultrasonography, and a mammary tumour that might have caused the hypoglycaemia, were identified. Because there was a high suspicion of non-islet cell tumour-induced hypoglycaemia as a paraneoplastic syndrome, the dogs underwent a hepatic lobectomy and total mastectomy with an ovariohysterectomy, respectively. Within 12 hours after surgery, the blood glucose concentrations of both cases had normalised, even without the administration of dextrose. The histopathological examinations identified a hepatocellular adenoma and a mammary carcinoma, respectively. The endocrine analysis of the serum at admission revealed low serum insulin concentrations (< 1.44 pmol/l) and high serum concentrations of insulin-like growth factor 2 in both dogs. Therefore, the diagnosis in both dogs was confirmed to be non-islet cell tumour-induced hypoglycaemia. Both dogs remained alive without the recurrence of hypoglycaemia 24 months later. Previously, the administration of intravenous dextrose has been considered as the initial treatment in dogs with hypoglycaemia; however, this can temporarily ameliorate the clinical signs related to the non-islet cell tumour-induced hypoglycaemia and help the anaesthesia for the surgical tumour resection as an emergency. Therefore, the definitive treatment of non-islet cell tumour-induced hypoglycaemia might be rapid surgical intervention, which can be associated with good prognosis in dogs with severe non-islet cell tumour-induced hypoglycaemia.

Battaglia L, Petterino C, Zappulli V, Castagnaro M (2005): Hypoglycaemia as a paraneoplastic syndrome associated with renal adenocarcinoma in a dog. Veterinary Research Communications 29, 671–675. https://doi.org/10.1007/s11259-005-3305-x
Beaudry D, Knapp DW, Montgomery T, Sandusky GS, Morrison WB, Nelson RW (1995): Hypoglycemia in four dogs with smooth muscle tumors. Journal of Veterinary Internal Medicine 9, 415–418. https://doi.org/10.1111/j.1939-1676.1995.tb03302.x
Boari A, Barreca A, Bestetti GE, Minuto F, Venturoli M (1995): Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide. European Journal of Endocrinology 132, 744–750. https://doi.org/10.1530/eje.0.1320744
Bodnar TW, Acevedo MJ, Pietropaolo M (2014): Management of Non-Islet-Cell Tumor Hypoglycemia: A Clinical Review. The Journal of Clinical Endocrinology and Metabolism 99, 713–722. https://doi.org/10.1210/jc.2013-3382
Bourcigaux N, Arnault-Ouary G, Christol R, Périn L, Charbonnel B, Le Bouc Y (2005): Treatment of hypoglycemia using combined glucocorticoid and recombinant human growth hormone in a patient with a metastatic non-islet cell tumor hypoglycaemia. Clinical Therapeutics 27, 246–251. https://doi.org/10.1016/j.clinthera.2005.02.004
Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service FJ, Endocrine Society (2009): Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology and Metabolism 94, 709–728. https://doi.org/10.1210/jc.2008-1410
Datte K, Guillaumin J, Barrett S, Monnig A, Cooper E (2016): Retrospective evaluation of the use of glucagon infusion as adjunctive therapy for hypoglycemia in dogs: 9 cases (2005-2014). Journal of Veterinary Emergency and Critical Care (San Antonio, Tex.: 2001) 26, 775–781.
de Groot JW, Rikhof B, van Doorn J, Bilo HJ, Alleman MA, Honkoop AH, van der Graaf WT (2007): Non-islet cell tumor-induced hypoglycemia: a review of the literature including two new cases. Endocrine-related Cancer 14, 979–993. https://doi.org/10.1677/ERC-07-0161
Dutta P, Aggarwal A, Gogate Y, Nahar U, Shah VN, Singla M, Khandelwal N, Bhansali A (2013): Non-islet cell tumor-induced hypoglycemia: a report of five cases and brief review of the literature. Endocrinology, Diabetes & Metabolism Case Reports 2013, 130046.
Dynkevich Y, Rother KI, Whitford I, Qureshi S, Galiveeti S, Szulc AL, Danoff A, Breen TL, Kaviani N, Shanik MH, Leroith D, Vigneri R, Koch CA, Roth J (2013): Tumors, IGF-2 and hypoglycemia: insights from the clinic, the laboratory and the historical archive. Endocrine Reviews 34, 798–826. https://doi.org/10.1210/er.2012-1033
Finotello R, Ressel L, Arvigo M, Baroni G, Marchetti V, Romanelli G, Burrow R, Mignacca D, Blackwood L (2016): Canine pancreatic islet cell tumours secreting insulin-like growth factor type 2: a rare entity. Veterinary and Comparative Oncology 14, 170–180. https://doi.org/10.1111/vco.12085
Fischer JR, Smith SA, Harkin KR (2000): Glucagon constat-rate infusion: a novel strategy for the management for the management of hyperinsulinemic-hypolglycemic crisis in the dog. Journal of the American Animal Hospital Association 36, 27–32. https://doi.org/10.5326/15473317-36-1-27
Idowu O, Heading K (2018): Hypoglycemia in dogs: Causes, management, and diagnosis. The Canadian Veterinary Journal 59, 642–649.
Koenig A (2015): 66 Hypoglycemia. In: Silverstein DC, Hopper K (eds): Small Animal Critical Care Medicine. 2nd edn. Elsevier, St. Louis. 352–357 p.
Lai JP, Chen ZM, Lok T, Chan OT, Himmelfarb E, Zhai Q, Lin F, Wang HL (2014): Immunohistochemical stains of proliferating cell nuclear antigen, insulin-like growth factor 2 and clusterin help distinguish malignant from benign liver nodular lesions. Journal of Clinical Pathology 67, 464–469. https://doi.org/10.1136/jclinpath-2013-201907
Lawson EA, Zhang X, Crocker JT, Wang WL, Klibanski A (2009): Hypoglycemia from IGF2 overexpression associated with activation of fetal promoters and loss of imprinting in a metastatic hemangiopericytoma. The Journal of Clinical Endocrinology and Metabolism 94, 2226–2231. https://doi.org/10.1210/jc.2009-0153
Leifer CE, Peterson ME, Matus RE, Patnaik AK (1985): Hypoglycemia associated with nonislet cell tumor in 13 dogs. Journal of the American Veterinary Medical Association 186, 53–55.
Loose NL, Rudloff E, Kirby R (2008): Hypoglycemia and its effect on the brain. Journal of Veterinary Emergency and Critical Care (San Antonio, Tex.: 2001) 18, 223–234.
Rivera N, Ramnanan CJ, An Z, Farmer T, Smith M, Farmer B, Irimia JM, Snead W, Lautz M, Roach PJ, Cherrington AD (2010): Insulin-induced hypoglycemia increases hepatic sensitivity to glucagon in dogs. The Journal of Clinical Investigation 120, 4425–4435. https://doi.org/10.1172/JCI40919
Rossi G, Errico G, Perez P, Rossi G, Paltrinieri S (2010): Paraneoplastic hypoglycemia in a diabetic dog with an insulin growth factor-2-producing mammary carcinoma. Veterinary Clinical Pathology 39, 480–484. https://doi.org/10.1111/j.1939-165X.2010.00260.x
Smith TA (1999): Facilitative glucose transporter expression in human cancer tissue. British Journal of Biomedical Science 56, 285–292.
Snead EC (2005): A case of bilateral renal lymphosarcoma with secondary polycythaemia and paraneoplastic syndromes of hypoglycaemia and uveitis in an English Springer Spaniel. Veterinary and Comparative Oncology 3, 139–144. https://doi.org/10.1111/j.1476-5810.2005.00069.x
Zeugswetter FK, Schornsteiner E, Haimel G, Schwendenwein I (2012): Metabolic and hormonal responses to subcutaneous glucagon in healthy beagles. Journal of Veterinary Emergency and Critical Care (San Antonio, Tex.: 2001) 22, 558–563.
Zini E, Glaus TM, Minuto F, Arvigo M, Hauser B, Reusch CE (2007): Paraneoplastic hypoglycemia due to an insulin-like growth factor type-II secreting hepatocellular carcinoma in a dog. Journal of Veterinary Internal Medicine 21, 193–195. https://doi.org/10.1111/j.1939-1676.2007.tb02946.x
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