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Canine Insulinoma
Veterinary & Aquatic Services Department, Drs. Foster & Smith
Liver and Pancreas
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Canine InsulinomaThis article will address the canine insulinoma, a cancerous growth that produces an over- abundance of the blood glucose regulating hormone, insulin.

Let's review some terms related to this discussion on canine insulinoma:

Cancer - A general term frequently used to indicate any of various types of malignant neoplasms (see below), most of which invade surrounding tissues, may metastasize (see below) to several sites, and are likely to recur after attempted removal and to cause death of the patient unless adequately treated.

Neoplasm - An abnormal tissue that grows by cellular proliferation more rapidly than normal and continues to grow after the stimuli that initiated the new growth ceases. Closely related to a tumor.

Tumor - An abnormal growth of tissue resulting from uncontrolled progressive multiplication of cells and serving no physiological function. Closely related to a neoplasm.

Malignant - Resistant to treatment; occurring in severe form, invades surrounding tissues and is frequently fatal.

Benign - Denoting the mild character of an illness or the non-malignant character of a neoplasm.

Metastatic - The shifting of a disease, from one part of the body to another. In cancer, the appearance of tumors in parts of the body remote from the origin of the primary tumor.

Chemotherapy - Treatment of disease by means of chemical substances or medications.

Exocrine gland - A gland that secretes a substance that ends up outside the body either directly or through a duct.

Endocrine gland - A gland that secretes a substance internally as into the bloodstream.

What is a canine insulinoma, where is one found and what affect does an insulinoma have on the dog?
The canine insulinoma is a cancerous growth located on or within the pancreas of the dog. The pancreas is a secretory organ that serves two main functions; as an exocrine gland and also as an endocrine gland. The exocrine portion of the pancreas produces digestive enzymes that allow the dog to break down proteins, carbohydrates and fats. These enzymes enter the duodenal portion of the small intestine via a small duct where they interact with food particles that are exiting the stomach.

The endocrine portion of the pancreas is located in several groups of cells located within the tissue of the pancreas called the Islets of Langerhans. These cells produce several different hormones; the most important for our discussion is insulin. Insulin is the 'truck' that 'carries' sugars, primarily glucose, from the bloodstream into the body's cells where it is used as the fuel that energizes the body, especially the brain. When blood sugar rises, after eating or in response to a stressful situation, insulin is released to deliver blood sugar to the cells. When the cells of the Islets of Langerhans become cancerous, they increase in numbers and the levels of hormones they produce also increase, in particular the dog's levels of insulin. When the dog's bloodstream receives an abnormally high level of insulin, the dog's available blood sugar is transported from the blood stream into cells markedly reducing the dog's blood sugar. This condition is called hypoglycemia. In response to hypoglycemia, the dog's body will release a number of hormones called catecholamines. These hormones attempt to counteract the hypoglycemia by mobilizing available sugars and sources of sugars.

Canine insulinoma's are almost always malignant and often metastatic.

What dogs are most commonly affected by insulinomas?
The average age when an insulinoma develops in a dog is nine years, with medium- to large-breed dogs most commonly affected.

What are the symptoms of insulinoma?
Dogs with an insulinoma demonstrate a variety of symptoms including:

  • Ataxia (incoordination)
  • Disorientation
  • Mental dullness
  • Visual disturbances
  • Seizures
  • Collapse
  • Death
These symptoms are the result of the insulin-induced hypoglycemia.

How is an insulinoma diagnosed?
A diagnosis of insulinoma requires several elements.

  • A persistent hypoglycemia is strongly suggestive. Multiple blood samples, fasting and non-fasting, may need to be evaluated.

  • Comparing the levels of insulin and glucose detected in the same blood sample can also be suggestive of an insulinoma. In this case, insulin levels would be above normal and glucose levels below normal.

  • A value called "the amended insulin: glucose ratio" may also be helpful. This test also compares the amount of insulin in the blood stream compared to the glucose levels. With this test, there may be a 'normal' insulin value with an abnormally low level of glucose.

  • Diagnostic imaging may or may not help in the diagnosis of this cancerous growth. Abdominal ultrasound of the pancreas is not typically helpful because of the small size of these cancerous lesions. Ultrasound may be helpful in examining other tissues for the presence of metastasis.

  • Visualizing the pancreas during abdominal surgery is considered the most definitive method of diagnosing an insulinoma. During abdominal surgery, the surgeon will gently palpate the pancreas for the presence of any abnormal growths. To help the surgeon see the insulinoma in the pancreas, a 1% solution of methylene blue stain mixed with saline is injected intravenously. The cells of the insulinoma will 'take-up' the stain while the surrounding tissue will not.

Will a canine insulinoma metastasize?
Yes, it is very likely that an insulinoma will spread to other parts of the dog's body. The most common sites for metastases include:

  • Regional lymph nodes
  • Duodenum
  • Liver
  • Mesentery
  • Spleen
As metastatic tumors grow, they often interfere with the function of surrounding structures and organs. For example, if the tumor develops on or near the duodenum, it may block the flow of digestive enzymes from the pancreas and/or bile from the gall bladder. Either of these situations will compromise the health of the dog.

Is a canine insulinoma treatable?
Yes, this tumor is treatable.

Early in the disease process, it is important that hypoglycemia be addressed by feeding several small meals throughout the day to help stabilize the dog's blood sugar. Medication such as corticosteroids can be used to help raise the blood sugar. Diazoxide may be used to inhibit insulin secretion.

Most often, treatment will involve surgically removing the insulinoma. It is critically important that hypoglycemia is controlled during and after surgery. Because the surgeon needs to manipulate the pancreas, the dog will need to be monitored for acute pancreatitis. Pancreatitis can be fatal.

If hypoglycemia persists after surgery, the prognosis is not as good. This would indicate that a portion of the insulinoma is still present and chemotherapy should begin.

There are several medications that can be used to suppress these tumors and their spread. Streptozocin attacks the beta cells directly, but it can have toxic side effects; toceranib and alloxan are additional options.

The primary goal of treatment is to stabilize the dog's blood glucose and avoid hypoglycemia. If the dog is experiencing seizures as a result of the hypoglycemia that cannot be controlled with diet and/or medications, the seizures may need to be controlled with a medication such as phenobarbital.

What is the prognosis for a dog with an insulinoma?
In most cases the prognosis for dogs with an insulinoma is guarded to poor. This tumor is almost always malignant and metastatic. Survival rates range from 6-24 months after the disease is diagnosed. Surgery, chemotherapy and diet can reduce the effects of the increase in insulin and the resulting decrease in blood glucose.

 
References and Further Reading

Goddard, L. Insulinoma: Why Is My Blood Sugar So Low? British Small Animal Veterinary Congress, Birmingham, United Kingdom, 2011.

Nelson, Richard W., Salisbury, Kathleen S. Pancreatic beta cell neoplasia. In Birchard, SJ; Sherding, RG (eds.) Saunders Manual of Small Animal Practice 2nd Edition. W.B. Saunders Co. Philadelphia, PA; 2000: 288-294.

Scott-Moncrieff, JC. Logical Approach to Diagnosis and Management of Hypoglycemia. Western Veterinary Conference, Las Vegas, NV 2011.

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