Gastrointestinal Endocrine Tumours
World Small Animal Veterinary Association World Congress Proceedings, 2014
Ninette Keller, BVSc, BVSc (Hons), MMedVet (Med) (Pret), Grad Cert Ed (JCU)
Veterinary Specialist Services, Gold Coast, QLD, Australia


Gastrointestinal (GI) endocrine disease occurs as a result of a tumour of one or more hormone-secreting cells in the GI tract. Tumours in this group include: insulinoma (beta cell tumour); amine precursor uptake and decarboxylation (APUD) tumours; gastrinoma (Zollinger-Ellison syndrome, delta cell tumour); glucagonoma (alpha cell tumour); VIPomas (Verner-Morrison syndrome); carcinoid tumours (Thorson-Bioerck syndrome or argentaffinoma syndrome); somatostatinomas and pancreatic polypeptidoma.

Most GI endocrine tumours are functional, and the clinical signs are related to the active substances secreted:

 Gastrinoma - gastrin

 Glucagonoma - glucagon

 Carcinoid tumours - serotonin

 Pancreatic polypeptidoma - pancreatic polypeptide

 Somatostatinomas - somatostatin

 VIPoma - vasoactive intestinal polypeptide

All these tumours are very rare. They mostly affect middle age to older dogs and cats. Only insulinomas, gastrinomas, glucagonomas and carcinoid syndrome/tumours have been reported in small animals. There is one report of a suspected case of pancreatic polypeptidoma in a cocker spaniel. Somatostatinomas and VIPomas have not been reported in dogs and cats.


Insulinoma, although rare, is the most common of all the gastrointestinal endocrine tumours. It is a functional tumour of the β cells of the pancreas causing excess secretion of insulin causing clinical signs related to profound hypoglycaemia. Insulinomas are mostly seen in middle-age to older dogs and are very rare in cats. Medium to large breeds appear mostly affected with increased incidence reported in Labrador Retrievers, Golden Retrievers, Boxers, Standard Poodles and Collies. Three of the six cats ever reported were Siamese cats.

Clinical Signs

In patients with insulinoma, the neoplastic β cells do not respond appropriately to the developing hypoglycaemia and continue to secrete insulin. The most commonly encountered clinical signs are seizures followed by weakness and collapse. The owners may have noticed episodes of ataxia, disorientation, muscle fasciculation and mental dullness before.


A complete history, full blood count, serum chemistry and urinalysis may be helpful to rule out other causes of hypoglycaemia (e.g., sepsis, hepatopathy, hypoadrenocorticism, xylitol toxicity, insulin overdose, etc.). Be aware that a normal blood glucose reading does not rule out insulinoma, as there are daily fluctuations. Insulin levels should be measured at the same time as when the blood glucose reading is below 3.2 mmol/l (60 mg/dl). Insulin secretion should be well below normal at this time. Therefore, a normal or high insulin reading at the same time of established hypoglycaemia is highly suggestive of insulinoma. If insulinoma is suspected but the patient's blood glucose readings are normal, then fast the patient and measure blood glucose every couple of hours. Once the blood glucose readings drop below 3.2 mmol/l, take a sample to measure the insulin levels at that time as well. Another way to establish chronic hypoglycaemia levels are by measuring fructosamine. Insulin/glucose ratios do not appear to help diagnostic accuracy.

Abdominal ultrasound of the pancreas may be helpful and has a reported accuracy of 30–75% of cases depending on the experience of the ultrasonographer. Fine-needle aspiration ultrasound guided of the lesion may confirm diagnosis. Abdominal CT or MRI scans have a 70% chance of making a diagnosis. Endoscopic ultrasound as used in humans has a reported sensitivity of 77–100% but is not readily available in veterinary practice. Contrast ultrasound has been shown to be effective, but large studies are not yet available.

Explorative laparotomy should be considered in patients that tick most of the boxes for insulinoma even if a mass is not seen on ultrasound or CT/MRI scan. Unfortunately, even this test has a poor reported sensitivity.

Treatment and Prognosis

Surgical removal of the tumour is the treatment of choice. In dogs, insulinoma develops with equal frequency in either lobe of the pancreas. The nodules are mostly solitary, but multiple nodules can occur. Insulinomas are highly malignant with up to 64% of cases having metastatic lesions at time of diagnosis. The liver, regional lymph nodes and omentum are the most common areas for metastases. Pancreatitis is a common complication post-surgery. Hypoglycaemia resolves almost immediately post successful surgery.

Recurrence of clinical signs is common due to the high rate of metastases. Small, high-protein meals fed frequently may help to control clinical signs. Exercise in these patients should also be limited. If diet alone is no longer enough to control clinical signs, then prednisolone or diazoxide (expensive) can be tried. Other treatments used with variable success include octreotide, streptozotocin and alloxan.

The median survival times for dogs are 12–14 months post surgery, with newer reports stating up to 1000 days (most likely due to earlier diagnosis). Younger dogs tend to have a shorter survival time, and in cats the reported survival time is 6 months.


Gastrinomas (Zollinger-Ellison syndrome) are uncommon APUD cell tumours that secrete excessive amount of gastrin causing hypersecretion of gastric acid. Gastrinomas have been diagnosed in both dogs and cats and mostly seen in middle age to older animals. They are mostly found in either the pancreas or duodenum, but can also be found in many ectopic sites including the stomach, jejunum, gall bladder and other.

Clinical Signs

Most of the signs are related to gastrointestinal ulceration and this includes vomiting, anorexia, weight loss, lethargy, polydipsia, haematomesis, melena and abdominal pain. If a gastrointestinal ulcer has ruptured, then signs of peritonitis and sepsis will be evident.


Finding a definitive diagnosis can be very difficult. A full blood count and serum chemistry may show nonspecific abnormalities (e.g., anaemia, hypoproteinaemia, hypokalaemia, etc.) related to chronic vomiting and diarrhoea.

Abdominal ultrasound may be helpful, but is often not conclusive. There may be evidence of thickening of the gastric wall/pylorus or signs of metastases in the liver or regional lymph nodes. Endoscopy is also nonspecific, but will confirm the presence of ulceration and may help to rule out other causes of haematomesis (e.g., Helicobacter infection).

An increase in fasting serum gastrin levels in humans has 98% sensitivity for diagnosing gastrinomas and appears to have similar results in dogs and cats. Other tests documented that may assist in a definitive diagnosis include: secretin or calcium stimulation test or 111iridium-octreotide test. Definitive diagnosis is made on histopathology of the tumour.


Treatment mostly resolves around treating and managing the gastric ulceration. This will include medical management with H2 (ranitidine or famotidine) or proton-pump inhibitors (omeprazole 0.5–1 mg/kg per day). Octreotide can also be tried. Surgery may also be needed especially when the ulcers have ruptured. Surgery to remove or debulk the tumours and metastatic lesions may help to alleviate the clinical signs, but is usually not curative. Chemotherapy has not been shown to be effective in gastrinomas. Survival times are very low due to high rate of metastasis of these tumours (median survival of 8 months).


Glucagonoma is a rare tumour of the alpha cells of the pancreas and causes an increased production of glucagon. Glucagonomas cause severe superficial necrolytic dermatitis as well as diabetes mellitus and all the associated clinical signs.

Full blood counts, serum chemistry and urinalysis are nonspecific and changes may include hyperglycaemia, increased liver enzymes and hypoalbuminaemia. Abdominal ultrasound may be helpful in finding a pancreatic nodule or even show metastases. Increased plasma glucagon concentrations and hypoaminoacidaemia are supportive of a diagnosis of glucagonoma. Definitive diagnosis is made on histopathology of skin lesions or a pancreatic nodule.

Surgery is often not curative due to high rate of metastases at time of diagnosis. Other forms of treatment include amino acid supplementation (eggs, prescription diets and IV amino acid infusion). Octreotide can also be tried.

Prognosis, as with most other GI endocrine tumours, is poor (mean of 5 months).

Carcinoid and Pancreatic Polypeptidoma

Carcinoid tumours are usually found in the ileum, but can occur throughout the gastrointestinal system and have also been reported in the lungs in nearly a third of all cases. Carcinoid tumours cause an increased secretion of serotonin. "Carcinoid syndrome" described in humans have not been reported in dogs or cats. Carcinoid syndrome is caused by carcinoid metastases and includes cutaneous flushing, bronchoconstriction and right-sided heart failure.

Full blood count and serum chemistry results are usually normal in patients with carcinoid tumours. Abdominal ultrasound may be helpful in finding the primary tumour or metastatic lesions. Confirmation requires exploratory surgery and histopathology.

Pancreatic polypeptidoma has only been reported in a 7-year-old female Cocker Spaniel. This tumour causes an increased secretion of pancreatic polypeptides. Clinical signs include chronic vomiting and diarrhoea. Diagnosis is based on increased levels of pancreatic polypeptides.

Treatment for both tumours includes surgical removal, but due to the high rate of metastases, surgery is often not curative. Medical management is needed to control the clinical signs. Octreotide can be used. Effective chemotherapy has not been reported. Streptozotocin has been used in humans with limited success.

Prognosis is poor for both conditions.


Gastro-endocrine tumours are rare and can be very difficult to diagnose. It is advisable to refer these cases to a specialist centre. Many of these tumours go undiagnosed due to our low levels of suspicion.


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Speaker Information
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Ninette Keller, BVSc, BVSc (Hons), MMedVet (Med) (Pret), Grad Cert Ed (JCU)
Veterinary Specialist Services
Gold Coast, QLD, Australia

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