insulinoma (beta cell)

INSULINOMA (Beta Cell Tumor)

Overview

One of the most common tumors in domestic ferrets, insulinoma is a cancer of the pancreatic islet or “beta” cells.   The pancreas produces many enzymes and hormones; pancreatic “beta” cells produce insulin, the hormone that regulates the body’s use of sugar, a form of carbohydrate.   Blood sugar comes from the dietary intake of carbohydrates (sucrose, fructose, glucose, dextrose, lactose – from fruits, vegetables, diary, honey, etc.; starch from grains, flour, potatoes, rice, etc.).   When blood sugar levels rise, the pancreas secretes insulin, which moves the sugar into body cells (brain, muscle, fat cells).  Cells use the sugar for energy.
 
Beta cells normally respond to the blood sugar (glucose) levels, turning out insulin when blood levels are high (“hyperglycemia”) and turning off insulin production when sugar blood levels are low (“hypoglycemia”).   Cancerous beta cells do not respond normal fluctuations, and so keep putting out insulin, resulting in dangerously low blood sugar levels.   Low blood sugar levels results in clinical changes or “signs.”   
 
[NOTE:  Diabetes is the condition where the pancreas puts out too little insulin, causing the blood sugar level to rise, or “hyperglycemia.”   Diabetes is relatively rare in ferrets.]  
 
Diagnosis is by Clinical Signs and Laboratory Confirmation
 
Clinical
Some ferrets may have a sudden onset of severe symptoms.  Occasionally, there are no obvious signs, and insulinoma is only discovered during lab testing done for other problems. Insulinoma can be found concurrently with adrenal tumors.  Although insulinoma tumors are often an incidental finding discovered at the time of surgery for another reason, most ferrets are diagnosed when they begin showing signs of low blood sugar:   staring spells, drooling (salivation), sleepiness (lethargy), clawing at the mouth (sign of nausea), loss of appetite.   This can lead to weight loss and loss of strength and coordination.  Hind-leg weakness is not uncommon.   When the hypoglycemia is severe, the ferret can experience seizures (often with high-pitched “scream” or “bark”), loss of consciousness, and become comatose.   This constitutes an emergency:  the ferret must receive sugar to reverse the signs.   
 
Diagnosis
Generally a blood glucose (sugar) test along with clinical signs are used to make the diagnosis of insulinoma. Normal fasted blood glucose levels in ferrets runs between 65 mg/dL to 112 mg/dL.  Levels A blood glucose level less than 70 mg/dL with clinical signs is suggestive of insulinoma.  Ferrets with a blood glucose level < 40 mg/dL may present lethargic, collapsed or comatose.   
 
Differential Diagnoses:  Other causes of hypoglycemia must be ruled out, such as loss of appetite, or inability to eat due to other reasons, including GI blockage, starvation, toxicity due to drugs or poisoning, etc.   
 
A definitive diagnosis of insulinoma can only be obtained from histopathological analysis of a surgical pancreatic biopsy.  Elevated blood insulin levels (using an assay that has been validated for ferrets) indicate insulinoma, although this test is rarely performed due to cost.  Neither of these diagnostic tests are generally performed due to cost considerations.
 
Treatments
 
Surgery:    Removal of the tumors.  If the ferret is experiencing clinical signs of hypoglycemia and is able to undergo surgery, this approach should be strongly considered.   Reasons for doing surgery: 

• Potential cure of the disease.  
• Relief of blockage from space-occupying tumors.  
• Other organs, such as the liver, can be inspected for signs of tumors.      

 
Medical Treatment:  Treatment with drugs and diet.   Medical therapy is considered palliative:  it controls the signs, but does not impact the tumor itself, which may continue to grow.    

• Drugs:   Prednisone/Prednisolone and Diazoxide, either alone or in combination [see BOX]
• Experimental drugs for ferrets:   Octreotide (somatostatin analogue) and others
• Diet:   Dietary management is a very important part of the overall treatment.   The ferret may require frequent feedings to maintain normal blood sugar levels.   The diet should be high in protein (minimum 32%) and fat (minimum 15%), but low in carbohydrates (see also:  NUTRITION).     
• Depending on the stage of disease found at surgery, drugs can be started following surgical removal of the tumor(s), or used when the ferret is not a surgical candidate (due to advanced age or other illnesses, such as heart disease, etc.).
• Severe hypoglycemia (lethargy, seizures, loss of consciousness) requires immediate supportive treatment:  IV or SC Dextrose and short-term (emergency) use of glucose and fluids must be used.  

Monitoring
 
Blood glucose is the best way to monitor the activity of beta cell function.  A drop of blood is placed on a glucose monitor.  The monitor gives a reading of the blood glucose level.  Glucose monitors can be purchased at pharmacies and online.   [see Glucose Monitors]
 
Emergency Treatment at Home
 
If your pet has an episode of hypoglycemia it should be given carbohydrate.   Products such as Karo® syrup, Nutrical® paste, honey, or other foods high in glucose can raise the blood sugar level temporarily.   Following a high sugar food, the ferret should be fed it its normal diet to minimize excess secretion of insulin.   If your ferret has collapsed and is unable to swallow, rub a small amount of honey or syrup on its gums.   Only use just enough to wet the gums and take care not to be bitten if your ferret is having a seizure. When it regains consciousness feed it its normal diet and bring it to the hospital for an examination, blood glucose check.   Intravenous Dextrose is required to treat very low blood sugar.
 
Prevention
 
In recent years, insulinoma has become less common most likely a result of a better understanding of the nutritional requirements of the ferret.   Commercial foods specially formulated foods now address the fact that the ferret is an “obligate carnivore” (requires meat).  Most diets now contain meat or meat by-products as the first three ingredients listed.  Many lower quality foods may have meat as the first ingredient, but grains or plant-based second or third ingredients, which have high carbohydrate content.   Also, ferrets should not be given non-meat based “treats.”  [The concept of “treats” is based on human needs – not ferret- nutrition!]   Ferrets should never be given foods or treats with high levels of carbohydrate, such as fruits-- raisins, cereal, or products made with flour or sugar.  These foods stimulate the beta cells to secrete more insulin, making the condition worse.
 
Disease Course and Prognosis
 
Although ferret insulinomas rarely spread (metastasize), as they can in dogs and cats, these tumors can still be deadly because they can cause dangerously low blood sugar levels. 
Insulinoma usually occurs in older ferrets, although younger ferrets can have the condition.   Signs usually start gradually, but get worse and more frequent with time.   
 
Surgical removal of tumor may result in a “cure”; however, many tumors are tiny and clinical signs may return within 8 to 12 months.  If the signs recur following surgical removal of the tumor(s), a repeat surgery can be considered.   Because medical management is only palliative, it can only control the hypoglycemia.  Over time, as the insulinoma progresses, the ferret’s condition will worsen, requiring increasing doses of the medication, until the drug(s) become ineffective or the ferret’s condition requires a decision.  In such cases it is important to consider the ferret’s quality of life and make a decision how long to continue treatment.  
 
References
 
Buchanan K, Belote D:  Pancreatic islet cell tumor in a domestic ferret.  Contemp Top Lab Anim Sci. 2003 Nov;42(6):46-8.
 
Pilny A & Chen S. [The Animal Medical Center - New York, NY]   Ferret Insulinoma: Diagnosis and Treatment.  VetLearn Compendium. Continue Education Article #4: pp- 722-729, 2004.  www.VetLearn.com [Accessed 2014]
 
Weiss C, Williams B, Scott M:  Insulinoma in the ferret: clinical findings and treatment comparison of 66 cases.  J Am Anim Hosp Assoc. 1998 Nov-Dec;34(6):471-5.
 
Williams, B:  Pathology of Insulinoma Ferret Insulinoma FAQ -  ` Information from several ferret veterinarians (including Dr. Bruce Williams) on insulinoma signs, diagnosis and treatment.​