be provided.
Insulinoma
Overview
Insulin secreting pancreatic β-islet cell neoplasia is the most common cause of hypoglycaemia-induced seizures in adult dogs. Feline insulinoma is rare. These tumours are associated with excess insulin secretion independent of the negative feedback effects caused by hypoglycaemia. Hyperinsulinaemia produces hypoglycaemia through suppression of glucose release and production rather than increased glucose utilization (Goutal et al., 2012). Most canine insulinomas are malignant. Metastatic lesions have been detected in 45% to 64% of dogs in different studies and most dogs have involvement of regional lymph nodes with or without distant metastases (commonly in the liver) by the time insulinoma is diagnosed (Hess, 2010). Insulinoma has been reported predominantly in adult to old dogs (mean age of 9 years) and in medium- to large-breed dogs.
Clinical presentation
Clinical signs are related to insulin-induced neuroglycopenia (seizures, generalized weakness, collapse, ataxia, obtundation and impaired vision) and/or to hypoglycaemia-induced catecholamine release (tremors, nervousness and hunger) (Goutal et al., 2012). Clinical signs can occur intermittently (Hess, 2010). Fasting, excitement or exercise can precipitate or worsen clinical signs by decreasing blood glucose concentration. Feeding can result in either alleviation (when restoring normoglycaemia) or exacerbation (by stimulating insulin secretion) of clinical signs (Hess, 2010). A peripheral polyneuropathy has been described in dogs with insulinoma and may be caused by an immune mediated paraneoplastic process or by glucose-mediated metabolic disturbances in the lower motor neurons.
Diagnosis
Neurological signs consistent with hypoglycaemia (blood glucose concentrations below 60 mg/dl or 3 mmol/l) and concurrent hyper-insulinaemia (serum insulin concentration greater than 20 μU/ml) are suggestive of insulinoma. When a dog suspected of having an insulinoma is normoglycaemic, it should be fasted under close observation and blood glucose concentration should be measured every 1 to 2 h. Most dogs with insulinoma would develop hypoglycaemia within 12 h of fasting. When hypoglycaemia (blood glucose concentration <60 mg/dl or <3mmol/l) is detected, blood should be collected for measurement of insulin concentration and the dog should then be fed (Hess, 2010). Some dogs require repeated insulin measurements to confirm the suspicion of insulinoma. In one study hyperinsulinaemia was detected in 76% of dogs with insulinoma when insulin was measured once and in 91% of dogs when insulin was measured twice (Leifer et al., 1986). Fructosamine concentration can help to detect chronic hypoglycaemia as this parameter reflects the blood glucose concentrations over the previous 1–2 weeks and it has been reported to be significantly decreased in dogs with insulinomas. The clinical diagnosis of insulinoma can be further supported by identification of a pancreatic mass with abdominal ultrasonography or contrast-enhanced computed tomography (Figs 4.1, 4.2a, b). The sensitivity of abdominal ultrasonography in detecting insulinoma ranges from 28% to 75% (Goutal et al., 2012). Contrast-enhanced ultrasonography may increase the diagnostic yield of ultrasound. Ultrasound-guided fine-needle aspirate cytology represents a relatively noninvasive tool to support the diagnosis of insulinoma. The definitive diagnosis is made following histological examination of the tumour after surgical resection.
Fig. 4.1. Ultrasonographic image of the right craniodorsal abdomen obtained using an intercostal approach in a 7-year-old, male boxer presented for seizures. An irregularly rounded 16 mm diameter hypoechoic nodule (between calipers) is present within the cranial aspect of the right limb of the pancreas. Note that in order to optimize the image of the nodule normal anatomic landmarks such as the duodenum (arrow) and the pancreatic vessels are only partly demonstrated in the image. (Photo courtesy of Andrew Halloway)
Fig. 4.2. Pre- and post-contrast CT images of the abdomen of a dog with an insulinoma in the left limb of the pancreas. On the pre-contrast image (a) the lateral aspect of the left limb of the pancreas is focally enlarged by a 15 mm diameter nodule (arrow). The nodule is slightly hypo-attenuating to adjacent normal pancreas. The post-contrast image (b) was obtained during the arterial phase of angiography. There is marked enhancement of the periphery and medioventral aspect of the mass. The dorsolateral aspect of the mass does not enhance (arrow). (Photo courtesy of Fraser McConnell, University of Liverpool)
Management
Emergency treatment of hypoglycaemia-induced seizures involves slow intravenous administration of 0.5–1 ml/kg of 50% dextrose, diluted 1:2 or 1:4 with sterile water, followed by an intravenous continuous rate infusion of 2.5–5% dextrose. Dextrose administration can be discontinued when clinical signs resolve.
Resolution of clinical signs may be difficult to achieve or to maintain in some dogs as the dextrose bolus may induce further insulin release from the tumour, leading to worsening of the hypoglycaemia. In such cases, repetitive dextrose boluses are not effective as a single strategy and either alternative or adjunctive therapies should be considered. These include: dexamethasone 0.1–0.5 mg/kg intravenously every 12 h, and glucagon at initial infusion rate of 5 ng/kg/min and subsequently adjusted based on blood glucose values up to 13 ng/kg/min. AEMs (see Chapters 12 and 24) may be necessary in severely affected cases. Frequent feeding of small meals should be initiated as soon as the animal can eat. Long-term treatment involves medical management (pre- and post-operatively or in dogs in which surgery cannot be performed) and surgical resection of the pancreatic mass and gross metastases. Whenever possible, surgical resection is considered the treatment of choice as despite being rarely curative, it offers the greatest chance of both durable control of clinical signs and prolonged survival time in dogs with insulinomas. However, outcome is affected by tumour staging. Some dogs can develop diabetes mellitus (transient or permanent) post-operatively. Medical management of insulinoma involves small frequent meals (every 4–6 h) of a diet rich in proteins, fat and complex carbohydrates, prednisolone 0.5 mg/kg/day orally (up to 4 mg/kg/day in refractory cases), and exercise restriction and avoidance of excitement. Additional medical therapy to relieve the hypoglycaemia may be required in some dogs and involves diazoxide 5 mg/kg every 12 h orally, which can be increased gradually without exceeding 60 mg/kg/day, or synthetic somatostatin such as octreotide (Goutal et al., 2012). Streptozotocin, a nitrosurea chemotherapeutic agent, can be used to selectively destroy beta cells in the pancreas or metastatic sites, but it can be nephrotoxic and emetogenic and its use in dogs warrants further investigations. At home immediate management of hypoglycaemic crisis involves oral administration of honey, corn syrup or maple syrup. Median survival time 12 to 14 months (range 0 days to 5 years) in dogs undergoing surgery in different studies. Whereas median survival ranges from 74 to 196 days in dogs undergoing medical treatment only. Combination of medical and surgical treatment resulted in a median survival time of 1316 days (44 months) in a recent study (Goutal et al., 2012).
Hepatic encephalopathy
Overview
Hepatic encephalopathy (HE) is a biochemical disorder of the brain secondary to various hepatic disorders such as congenital and acquired portosystemic shunt, micro-vascular dysplasia, congenital urea-cycle enzyme deficiencies, and acute or chronic severe parenchymal liver damage associated with cirrhosis, neoplasia, chronic active
