Insulinoma

Insulinoma is a type of cancer which affects the pancreas. The disease develops from mutations in the gene called INS (insulin dependent) or IR (insulin receptor). Insulinoma occurs when cells become resistant to insulin’s effects. Insulin resistance leads to diabetes mellitus, an illness characterized by excessive blood sugar levels and associated complications such as blindness, kidney failure, heart attack and stroke. Diabetes is usually diagnosed after symptoms develop.

In insulinoma, there are two types: Type 1 and Type 2. Type 1 is rarer than type 2. Both forms of the disease have similar features but different characteristics.

There are many possible causes of insulinoma including genetic defects, environmental factors like smoking, infections and autoimmune diseases. Some of these conditions may cause other problems such as liver damage or pancreatic cancer.

The most common form of insulinoma is Type I which accounts for approximately 80% of cases in dogs. Type I insulinomas are usually found in young adult dogs with no family history of the disease. Other risk factors include obesity, renal insufficiency, hepatic dysfunction due to alcohol abuse or chronic hepatitis B infection.

These conditions increase the risk of developing Type 1 insulinoma.

Type II insulinomas occur less frequently but they do exist. They account for 20% of all cases in dogs and account for 60% of all cases in cats. The most common breeds to develop these tumors are German Shepherds, Miniature Pinschers, Keeshonds, Great Danes, and Boxers.

Insulinomas can affect any breed of dog or cat of any age. They usually have an average life span of 3-10 years of age but can live for a few years longer or shorter. Some animals may suffer from more than one tumor, but usually they do not spread or metastasize.

As pets age, there is an increase risk of developing neoplasms and pancreatic adenocarcinoma. These tumors are usually malignant and rarely occur in younger animals. There is a strong link between the development of insulinomas and other endocrine tumors (tumors that produce hormones).

The most common is Cushing’s disease or hyperadrenocorticism. All of these conditions may increase the risk of developing liver disease and pancreatic cancer.

There are various symptoms of this disease that may present at any time during the course of the disease. The symptoms depend on the size and number of tumors in the pancreas and if the tumors have spread to other organs. Dogs may show increased or decreased appetite, vomiting, diarrhea, weight loss, dehydration, weakness, paralysis of facial muscles, abdominal masses, dullness, collapse, jaundice and labored breathing.

Cats usually don’t show many external symptoms besides jaundice, restlessness, irritability, weakness and labored breathing. In severe cases of advanced tumors, gastric outlet obstruction may occur.

The diagnosis of this condition is based on medical history, clinical signs and diagnostic tests. A complete blood profile will be conducted to determine the health of the animal and look for signs of infection or other medical problems. The white blood cell count may be elevated if there is an infection.

The biochemical profile may show signs of pancreatitis, liver disease or even kidney malfunction. Hyperlipidemia (elevated fat deposits in the blood) may also be found during the biochemistry profile.

Radiographs may be taken to check for abdominal mass or gastric dilation. This is usually only performed if there are physical signs that suggest these problems. Ultrasound and CAT Scans may be used to determine if there are any masses in the pancreas or if there are signs of gastric dilation.

The definitive diagnosis is usually made with an electrosurgical biopsy. This procedure uses heat to burn a small piece of tissue from the mass for analysis under a microscope. If the tumor is non-cancerous (benign), then no further treatment will be necessary unless the dog shows clinical signs. If the tumor is malignant and has spread to other organs, chemotherapy and radiation therapy may be necessary.

The prognosis for dogs with non-cancerous or benign tumors is good. The prognosis for dogs with malignant tumors is not as good and will depend on whether or not the cancer has spread to other organs. Chemotherapy and radiation therapy are not usually very effective in animals but they do provide some relief and extend the life span of the animal.

Tumors of the pancreas are usually diagnosed in older dogs and in breeds such as the German Shepherd, Doberman Pinscher, Great Dane, Saint Bernard, Boxer and the Scottish Terrier.

Tumors of the exocrine pancreas usually develop slowly over a period of months or years. The average age is around 7 years old. The most common type of tumor is an insulinoma.

Insulinomas produce excess amounts of the hormones insulin and sometimes glucagon. These hormones are used in the regulation of blood sugar, digestion and many other important bodily functions. Most tumors are benign, but they can be malignant and though rare, can spread to other parts of the body.

Insulinomas can be classified by their location within the pancreas. Most are located in the head, or distal 1/3 of the pancreas. Others are located in the body or proximal 2/3 of the pancreas.

Insulinomas often lead to an increase in appetite known as cravings. The most common symptoms are related to the digestive system such as:

Vomiting

Loss of Appetite

Diarrhea

Dehydration

These symptoms tend to come and go. There are also many other possible symptoms depending on the dog’s age, breed and gender. Some of these include: Seizures, Weakness, Intestinal Impaction, Diabetic Ketoacidosis (common in dogs with insulinomas), Coma and Death.

Insulinomas are usually diagnosed with a combination of medical history, physical examination, lab work and diagnostic tests.

There are some steps you can take at home to help control your dog’s symptoms and to keep him as comfortable as possible. This includes feeding a high quality diet and making sure he gets plenty of other nutritious snacks throughout the day. These snacks should consist of carbohydrates and proteins since insulinomas tend to increase the dogs hunger and the snacks will help decrease some of the digestive issues.

Probiotics such as yogurt and other foods that contain “live” active cultures help to keep the digestive system healthy by increasing the good bacteria within the intestines. Vitamin supplementation can also be helpful. A multivitamin such as Nutrical or EssentialEvo can be given once or twice a day. Another supplement known as Pancrease(r) can also be given twice a day. This contains the enzymes lipase and protease which help with proper digestion of fats and proteins.

There are also some steps you can take to provide your dog relief from the symptoms. These include:

For Diarrhea-Loperamide (Imodium(r)) at 2mg per pound of body weight up to 4 times a day.

For Vomiting-Ondansetron (Zofran(r)) at 4mg per pound of body weight as needed.

For Weakness-Parenteral nutrition (PN) through injection or Subcutaneous Nutritional Infusion (SQ). PN provides required nutrients that cannot be obtained from food due to the loss of the digestive tract or malabsorption issues.

PN is time and labor intensive, expensive and must be administered by a licensed veterinarian.

SQ is less expensive and time consuming to set up. It provides many of the same benefits as PN, but not all. It can be set up at home with directions from your veterinarian.

It can also be used in conjunction with PN to help decrease some of the time and financial demands.

PN is a treatment modality in which all of the dog’s required nutrients are given to him intravenously.

Insulinomas are one of the most common tumors in dogs. The good news is that most insulinomas are benign and insulinoma treatment is very successful. The bad news is that some insulinomas are malignant and can they can be fatal if left untreated.

The average cost of an insulinoma surgery is between $1,500-$2,000.

There are several medications that can be useful in treating insulinomas. Most of these must be given by injection and some may be difficult to acquire.

Glucophage(r) improves the ability of the pancreas to produce insulin.

Diazoxide(r) decreases the production of insulin by the pancreas.

Octreotide(r) helps decrease the secretion of glucagons and somatostatin which stimulates insulin release.

Dopamine(r) stimulates the release of insulin from the pancreas.

Most cases of acromegaly can be cured through surgery. After the initial surgery; radiation therapy, octreotide(r), diazoxide(r), or chemotherapy may be necessary to further treat the disease and prevent further growth of the tumor.

The most common type of treatment is surgery. The initial surgery is usually to remove the tumor. During this time the physician will take biopsies of the tumor to examine under a microscope and determine the type of tumor it is and therefore the best way to treat it.

The three most common methods to treat acromegaly are:

1) Radiation therapy- uses x-rays or other types of radiation to kill the cancer cells.

2) Chemotherapy- uses drugs to stop the growth of cancer cells.

3) Surgical debulkment- surgery used to remove as much of the tumor as possible.

Glossary

Acromegaly: A disorder that occurs when a benign tumor forms on the melonsecreting anterior pituitary. This form of the disease causes gigantism in children and leads to all the physical problems of giantism after the child has stopped growing.

Anterior pituitary: The front portion of the pituitary gland.

Atom: The smallest possible portion of an element.

Benign: Not cancerous.

Cancer: An uncontrolled division of cells that have mutated and no longer function properly.

Carbohydrates: One of the three macronutrients needed by the body. Provides energy in the body.

Catalase: An enzyme that breaks down hydrogen peroxide into water and oxygen.

Dative: Denotes two objects directly affected by a verb.

Diabetes: A disorder in which the body is unable to regulate the amount of sugar in the blood.

Euthanize: To put an animal to sleep in order to prevent suffering from an incurable disease or injury.

Fat: One of the three macronutrients needed by the body. Stores energy in the body.

Glucose: A simple sugar which is used by the body as a source of energy.

Ion: An atom that has either lost or gained one or more electrons.

Isotope: Atoms of the same element that have a different number of neutrons.

Leprosy: A disease caused by Mycobacterium leprae which attacks the skin, nerves, eyes, and lungs.

Magnetic Resonance Imaging (MRI): A procedure in which a powerful magnet is used to take a picture of the internal organs of the body.

Malignant: Cancer which can spread to other parts of the body.

Melanin: A brown pigment that lends color to skin, hair, and eyes.

Metastasis: The process by which cancer spreads to other parts of the body.

Neurotransmitter: A chemical that sends messages between nerve cells.

Nucleus: (

1) The center of an atom.

(

2) The center of a cell.

Oncology: Branch of medicine that deals with tumors and cancer.

Pancreas: A gland located behind the stomach which secretes enzymes to aid in the digestion of food and insulin to regulate blood sugar levels.

Pathogen: A germ or other agent that causes disease.

Sources & references used in this article:

Insulinoma by CS Grant – Best practice & research Clinical gastroenterology, 2005 – Elsevier

Diagnosis and management of insulinoma by T Okabayashi, Y Shima, T Sumiyoshi… – World journal of …, 2013 – ncbi.nlm.nih.gov

Insulinoma by A Mathur, P Gorden, SK Libutti – Surgical Clinics, 2009 – surgical.theclinics.com

The management of insulinoma by ON Tucker, PL Crotty, KC Conlon – British Journal of Surgery, 2006 – ingentaconnect.com

A transplantable insulinoma in the rat by WL Chick, S Warren, RN Chute… – Proceedings of the …, 1977 – National Acad Sciences

Well-differentiated pancreatic tumor/carcinoma: insulinoma by WW De Herder, B Niederle, JY Scoazec… – …, 2006 – karger.com

Pancreatic insulinoma: current issues and trends by D Vaidakis, J Karoubalis, T Pappa… – Hepatobiliary & …, 2010 – airitilibrary.com

Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma by C Larsson, B Skogseid, K Öberg, Y Nakamura… – Nature, 1988 – Springer

Functioning insulinoma—incidence, recurrence, and long-term survival of patients: a 60-year study by FJ SERVICE, MM McMAHON, PC O’BRIEN… – Mayo Clinic …, 1991 – Elsevier