Insulinoma in Dogs

Overview of Canine Insulinoma

An insulinoma is a malignant tumor of the pancreas that secretes excessive amounts of insulin leading to hypoglycemia (low blood sugar concentration). Insulinomas usually occur in middle-aged to older dogs, usually eight to twelve years of age. They are very rare in cats and there is no apparent gender predilection.

Insulinomas can occur in any breed of dog with mixed breed dogs most commonly affected. Among purebred dogs, Irish setters, German shepherds, boxers, golden retrievers, poodles, and Labrador retrievers have a higher incidence. Medium to large-sized breeds of dogs are most commonly affected.

The excessive secretion of insulin by these tumors causes hypoglycemia and clinical symptoms of hypoglycemia.

What to Watch For

• Seizures
• Collapse
• Fainting (also called syncope)
• Generalized weakness
• Hind limb weakness
• Lethargy
• Incoordination
• Muscle tremors
• Unusual behavior
• Polyphagia or increased appetite
• Exercise intolerance
• Shaking
• Trembling
• Nervousness
• Dilated pupils
• Blindness

Diagnosis of Insulinoma in Dogs

Diagnostic tests are needed to identify insulinoma and exclude other diseases. Your veterinarian may recommend the following:

• A complete blood count (CBC or hemogram) to identify infection, inflammation, anemia, or low platelet count
• Serum biochemistry tests to identify hypoglycemia, evaluate your pet’s general health and determine the effect of the insulinoma on other body systems
• Urinalysis to evaluate kidney function and identify urinary infection
• Serum insulin concentration paired with blood glucose concentration. The hallmark of insulinoma is the presence of a normal or high serum insulin concentration at the same time that the patient has a low blood glucose concentration. In patients with hypoglycemia from other causes, serum insulin concentrations usually are very low at the same time the patient is hypoglycemic.
• Chest X-rays to determine if the insulinoma has spread to the lungs – a very rare occurrence
• Abdominal X-rays to evaluate liver, spleen, and kidneys. Insulinomas are very small and cannot be identified on plain X-rays of the abdomen.
• Abdominal ultrasound to evaluate the pancreas for presence of an insulinoma and the liver and abdominal lymph nodes for local spread of the insulinoma. Regional lymph nodes and liver are the most common sites for spread of insulinoma.

Treatment of Insulinoma in Dogs

Treatment for acute insulinoma may include the following:

• Surgery to remove the tumor
• Medical therapy
• Emergency treatment with intravenous glucose to increase the patient’s blood glucose concentration

Long-term treatment:

• Dietary therapy
• Cortisone-like drugs like prednisone
• Diazoxide, which is a drug that inhibits release of insulin from the insulinoma
• Somatostatin
• Chemotherapy, although it is not very effective for insulinoma

Home Care and Prevention for Insulinoma

Administer as directed any medications prescribed by your veterinarian and follow any special dietary recommendations. Watch your dog carefully for signs of hypoglycemia and administer corn syrup orally if you see signs of hypoglycemia, such as seizures, weakness or muscle tremors.

Observe your dog’s general activity level, appetite and attitude. Watch for recurrence of clinical symptoms of hypoglycemia that may indicate recurrence of the tumor. Feed frequent small meals of a high carbohydrate diet to maintain adequate blood sugar concentration.

Schedule regular follow-up visits with your veterinarian to monitor your dog’s progress and promptly identify any recurrence of hypoglycemia and insulinoma.

Keep your dog’s exercise and activity level relatively constant. Avoid intensive exercise or provide high carbohydrate snacks before exercise.

The cause of insulinomas is unknown, and consequently there is no way to prevent development. You can prevent a hypoglycemic crisis by following the dietary, exercise, and medical recommendations of your veterinarian.

Information In-depth for Insulinoma in Dogs

The pancreas contains collections of cells called islets of Langerhans. Normal islets contain four cell types: alpha, beta, delta, and F cells. Each of these cell types produces a specific hormone. Beta cells produce insulin. Excessive amounts of insulin are released into the bloodstream when a malignant tumor (insulinoma) develops from the beta cells. In normal animals, insulin works with other hormones to maintain blood sugar concentration in the normal range (approximately 70 to 100 milligrams per deciliters of blood). Excessive secretion of insulin by the beta cell tumor (insulinoma) causes the blood sugar concentration to fall below the normal range (hypoglycemia) with several different possible symptoms including:

• Seizures. Seizures are the most common symptom in dogs with insulinomas and occur in 68 percent of affected dogs.
• Generalized weakness
• Collapse or fainting (also called syncope)
• Hind limb weakness
• Lethargy
• Incoordination
• Muscle tremors
• Excessive food consumption, also called polyphagia. Presumably dogs eat more in an attempt to maintain their blood sugar concentration in the normal range.
• Exercise intolerance
• Weight gain due to the growth-promoting (or anabolic) effects of insulin

Most dogs with insulinomas display some of the symptoms listed above, but these symptoms tend to be intermittent and physical examination at the veterinarian’s office usually is unremarkable. Other medical problems can lead to symptoms similar to those encountered in insulinoma. It is important to exclude these conditions before establishing a definitive diagnosis:

• Some non-pancreatic tumors also can cause low blood sugar concentration, especially liver tumors, called hepatomas. There are several potential explanations why other tumors may cause low blood sugar concentration, including excessive glucose utilization by a very large tumor or secretion of a substance that mimics insulin in its effects.
• Severe liver disease. The liver is a major storage site for glucose. Hypoglycemia may develop in advanced or severe liver disease when more than 70 percent of the liver is compromised.
• Sepsis. Severe body-wide bacterial infection with widespread dissemination through the bloodstream may cause hypoglycemia, possibly due to increased utilization of the glucose by the bacteria.
• Insulin overdose. Hypoglycemia may occur as a result of an accidental overdose of insulin in a diabetic animal.
• Hypoadrenocorticism. Inadequate cortisol production by the adrenal glands, also called Addison’s disease, may result from inadequate production and mobilization of glucose.
• Hunting dog hypoglycemia. This poorly understood condition of nervous, thin hunting dogs may result in depletion of glucose stores in the liver and development of hypoglycemia.

Veterinary care should include diagnostic tests and subsequent treatment recommendations.

Diagnosis In-depth of Insulinoma in Dogs

Diagnostic tests are needed to recognize insulinoma and exclude other diseases. Tests may include:

• History and physical exam. Your veterinarian will take a complete medical history and perform a thorough physical examination and will carefully examine the abdomen to test for abdominal pain and abdominal masses. Insulinomas are typically very small and cannot be palpated.
• A complete blood count (CBC or hemogram) to evaluate for infection, inflammation, anemia, and low platelet count
• A serum biochemical profile to identify hypoglycemia, evaluate the general health of your dog and determine the possible effects of insulinoma on other body systems
• Urinalysis to evaluate your dog’s kidney function and check for urinary tract infection
• Concurrent evaluation of serum insulin and blood glucose concentrations. The single most reliable test for the diagnosis of insulinoma is the finding of an inappropriately high serum insulin concentration in an animal with hypoglycemia. The animal may be fasted until blood glucose concentration decreases to below 70 milligrams per deciliter of blood. At that time, a blood sample is sent to the laboratory for measurement of serum insulin concentration.
• Abdominal ultrasound examination to identify masses within the pancreas. Insulinomas are typically very small and only a small percentage of them can be identified during ultrasound examination. Other organs and abdominal lymph nodes can be assessed to see if the insulinoma has spread beyond the pancreas. The ultrasound examination should be performed by someone experienced in ultrasonography, and referral to a specialty center is often necessary.

Treatment In-depth for Dogs with Insulinoma

Treatment of acute insulinoma must be individualized based on the severity of your dog’s condition and other factors that must be analyzed by your veterinarian. Treatments may include surgery, medical management, or a combination of both.

Surgical removal

Surgery is usually the first approach to management and allows the possibility of cure for a dog with a single, easily removable tumor. Unfortunately, the tumor has usually spread to other abdominal sites, often the liver and regional lymph nodes, by the time a diagnosis is made, and surgery is only a temporary help. If the entire tumor is not removable, or if there has been spread to other organs, removal of as much abnormal tissue as possible usually results in remission of the symptoms of hypoglycemia and improves the response to medical therapy.

Medical therapy

• Emergency treatment at home. If your dog is having a hypoglycemic seizure, administer a sugar solution, such as Karo syrup or sugar water by mouth. Do not pour the sugar solution directly into your dog’s mouth, because the normal swallowing reflex may be impaired during the seizure and aspiration of the solution into the lungs could occur. Instead, dip your fingers into the sugar solution and rub it onto the gums and inside the mouth of your pet. Most pets will respond within 30 seconds to 2 minutes. Avoid placing your hand directly in your dog’s mouth because you may be inadvertently bitten due to involuntary jaw movements during a seizure.
• Emergency treatment in the hospital. If your dog has a seizure in the hospital, your veterinarian will administer a glucose solution, often 25 to 50 percent dextrose, intravenously to control the clinical signs of hypoglycemia. After the seizure has been controlled, further diagnostic testing and long-term therapy can be considered.

Long-term therapy

Long-term medical therapy is instituted if surgery is declined, the tumor cannot be completely removed or the tumor has spread to the liver and regional lymph nodes. Also, if a large amount of the tumor was removed surgically and clinical symptoms were controlled initially but have now reappeared, long-term therapy should be initiated, consisting of:

• Dietary therapy. If a constant source of calories is provided as a substrate for the excessive insulin, hypoglycemia and its associated clinical symptoms can be minimized. Diets high in protein, fat, and complex carbohydrates are recommended. Feed a combination of canned and dry food in several small meals throughout the day. Exercise should be limited to short leash walks. Simple sugars such as those found in soft-moist dog foods should be avoided because they rapidly stimulate insulin secretion.
• Glucocorticoids (cortisone-like drugs). When dietary manipulations alone are not effective in preventing signs of hypoglycemia, glucocorticoids should be administered. A glucocorticoid such as prednisone is given at a dosage of 0.12 mg per pound of body weight twice a day. This dosage is continued as long as it controls the clinical symptoms. If symptoms return, consult your veterinarian. Your veterinarian will instruct you on how to increase the dosage of prednisone to control the clinical symptoms. Dogs may develop adverse effects as a result of prolonged and excessive glucocorticoid treatment (excessive water consumption, increased urinations, increased appetite, panting, weight gain, hair loss). If these effects occur, your veterinarian may lower the dosage of prednisone and add diazoxide.
• Diazoxide inhibits the secretion of insulin from beta cells. It also stimulates the liver to produce more glucose. The end result is a rise in the blood sugar concentration. Administration of the diuretic hydrochlorothiazide may potentiate the effects of the diazoxide, and the two drugs may be administered together if diazoxide alone is ineffective. Unfortunately, diazoxide is fairly expensive and is difficult to obtain.
• Somatostatin. Somatostatin is a hormone made by the pancreas that inhibits the synthesis and secretion of insulin by normal and malignant beta cells. Its inhibitory action on insulin secretion can be maintained for several hours it is injected subcutaneously (under the skin). Not all dogs respond well to somatostatin and some dogs respond initially but become refractory later. Your veterinarian can teach you how to give subcutaneous injections of somatostatin if necessary.
• Chemotherapy. Specific chemotherapy agents have been tried, but many of these drugs are very toxic and the results have been poor.
• Streptozotocin selectively destroys pancreatic beta cells. It can cause severe kidney damage unless intensive intravenous fluid therapy is provided first. It is an investigational drug, and owners should provide informed consent before its use. The estimated success rate in insulinoma using streptozotocin is 30 percent.
• Alloxan also is toxic to pancreatic beta cells, and it also can cause severe kidney damage in dogs. A study of eight dogs showed initial control of hypoglycemia in four dogs for several months, but hypoglycemia eventually recurred in the four dogs that responded.
• Adriamycin has been effective in some human patients with insulinoma, but its efficacy for insulinomas in veterinary patients is not known.

Follow-up Care for Dogs with Insulinoma

Optimal treatment for your dog requires a combination of home and professional veterinary care. Follow-up can be crucial. Follow-up for insulinoma often includes the following:

• Administer as directed any medications prescribed by your veterinarian and contact your veterinarian promptly if you have difficulty treating your pet.
• Follow dietary recommendations made by your veterinarian. Dogs with insulinoma often are placed on diets high in protein, fat, and complex carbohydrates fed frequently as small meals.
• Blood sugar concentration should be monitored. Development of hypoglycemia often indicates a return of the tumor or spread to regional lymph nodes or liver.
• The long-term prognosis for pets with insulinoma is poor, but short-term prognosis is good. An average survival time of one year was found in one study of 114 dogs with insulinoma treated by surgery followed by medical therapy when symptoms recurred. Occasionally, dogs with insulinoma will live as long as two years after diagnosis and treatment. The survival rate may in fact be even better, since 31 of the dogs were still alive at the conclusion of the study.