Beta cells comprise 60% to 70% of pancreatic islet cells. Insulinomas have been shown to produce various polypeptides (somatostatin, glucagon, serotonin and pancreatic polypeptide). Most patients only have clinical signs of hyperinsulinism.
The clinical signs of hypoglycemia often seen after fasting, exercise, excitement, and eating, and are rapidly alleviated by the administration of glucose. Symptoms become more frequent as the disease progresses and are the result of both decreased glucose supply to the brain and stimulation of the counter-regulatory sympathoadrenal system. Signs include those related to hypoglycemia (lethargy, seizures and ataxia) and adrenergic effects (tachycardia, tremors, nervousness and polyphagia).
A tentative diagnosis can be made on laboratory evidence of persistent hypoglycemia (< 3.3 mmol/L) supportive by ultrasonographic, CT or MRI imaging showing a central abdominal tumor.
A definitive diagnosis of insulinoma is made following laboratory demonstration of an inappropriately high serum insulin concentration during a time of hypoglycemia (typically > 71.7 pmol/L). Insulin detection usually requires ELISA assaying by a reference laboratory.
Histological biopsies of the pancreas are usually confirmatory. Clinical staging is usually performed for prognositcation.
- Stage I - Insulinoma confined to pancreas
- Stage II - Insulinoma with metastasis to regional lymph node
- Stage III - Insulinoma with metastasis to distant organs
A differential diagnosis would include hypoglycemia of extrapancreatic tumors which secrete insulin-like hormones, including hyperinsulinism, hepatic dysfunction, adrenocortical insufficiency, hypopituitarism, extrapancreatic tumors, starvation, and sepsis.
Treatment of acute hypoglycemia requires intravenous administration of 2.5% to 5% dextrose in parenteral fluids, such as 0.9% NaCl or Ringer’s solution. Dogs that are convulsing should be given IV 0.5 g/kg dextrose slowly over 5 minutes.
Surgical treatment invariably requires pancreatectomy, and surgery is generally considered to be palliative, as microscopic metastases are usually present even when there are no visible metastatic lesions. Postoperative complications included pancreatitis, persistent hypoglycemia, hyperglycemia and diabetes mellitus, pancreatic pseudocyst, acquired seizures unrelated to hypoglycemia, and diffuse peripheral neuropathy.
Medical management includes a change in diet to a high protein, high fat, and complex carbohydrate diet, feeding small meals 3 to 6 times a day. Exercise restriction is important to minimize potential hypoglycemia episodes.
Chemotherapy is often indicated, due to the metastatic nature of this disease. Drugs include
- prednisolone - stimulates hepatic glycogenolysis while inhibiting insulin effects on peripheral tissues)
- diazoxide - antihypertensive that controls hypoglycemia
- octreotide - still under debate
Dogs with tumors confined to the pancreas (stage I) or with metastasis to regional lymph nodes (stage II) have a median survival time of approximately 1 - 2 years after surgery, whereas dogs with distant metastasis (stage III) have a median survival time of less than 6 months after surgery.
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