Islet cell tumors are the most common cause of hypoglycemia in older dogs. Clinical signs vary but often consist of weakness, ataxia, collapse and seizures. Diagnosis is by documenting hypoglycemia in conjunction with inappropriate insulin concentrations (normal or elevated) and elimination of other causes of hypoglycemia. Treatment options include palliative care (frequent feedings and prednisone), surgery, and chemotherapy. Long-term prognosis is generally less than 1 year survival.
The most frequent pancreatic islet tumor is an islet cell carcinoma derived from insulin-secreting β cells. These neoplasms frequently are hormonally active and secrete excessive amounts of insulin, which causes hypoglycemia. Endocrine pancreatic tissue appears to be derived from multipotential ductal epithelial cells, which differentiate into one of the several cell types present within the islets. Gastrin, somatostatin, pancreatic polypeptide, and vasoactive intestinal peptide may also be produced in excess in islet cell tumors. β-cell neoplasms of the pancreatic islets (insulinomas) are seen most frequently in dogs 5–12 years old. They are common in ferrets and have also been less frequently reported in cats and in older cattle.
Clinical Findings of Islet Cell Tumors
Clinical signs of insulinomas result from excessive insulin secretion, which leads to an increased rate of transfer of glucose from the extracellular fluid to body tissues and thus to severe hypoglycemia. The clinical signs are a reflection of the hypoglycemia and are not specific for hyperinsulinism associated with β-cell neoplasms. Dogs are easily agitated, and there are intermittent periods of excitability and restlessness. Periodic seizures may occur, and episodes of collapse resembling syncope have also been reported.
Initial clinical signs include:
posterior weakness
fatigue
generalized muscular twitching and weakness
ataxia
mental confusion
Clinical signs are characteristically episodic and occur initially at widely spaced intervals but become more frequent and prolonged as the disease progresses. Hypoglycemic attacks may be precipitated by physical exercise (increased use of glucose) or fasting (decreased availability of glucose) as well as by ingestion of food (stimulation of insulin release). Administration of glucose rapidly alleviates the signs.
The predominance of clinical signs relating to the CNS demonstrates the primary dependence of the brain on the metabolism of glucose for energy. When the brain is not supplied with glucose, cerebral oxidation decreases and manifestations of anoxia appear. Because clinical signs are compatible with primary disease of the CNS, functional islet cell tumors may be misdiagnosed as idiopathic epilepsy, brain tumors, or other organic neurologic disease. Repeated episodes of prolonged and severe hypoglycemia may result in irreversible neuronal degeneration throughout the brain. Permanent neurologic disability probably accounts for the terminal coma, unresponsiveness to glucose, and eventual death of some dogs.
Lesions
Courtesy of Dr. Sean Aiken.
Insulinomas usually appear as single, yellow to dark red, spherical, small (1–3 cm) nodules visible from the serosal surface. They occur as single or occasionally multiple nodules in the same or different lobes of the pancreas. They are of similar consistency to or slightly firmer than the surrounding pancreatic parenchyma. A thin layer of fibrous connective tissue separates the neoplasm from the adjacent parenchyma. Insulinomas frequently metastasize to regional lymph nodes or the liver (or both) before diagnosis. True benign adenomas of islet cells are rare.
Diagnosis of Islet Cell Tumors
Demonstration of fasting hypoglycemia (≤60 mg/dL) with a normal or elevated serum insulin concentration.
A blood glucose determination should be done on all older dogs with a history of periodic weakness, collapse, or seizures. Fasting hypoglycemia (≤60 mg/dL) in a middle-aged to older dog is a strong indication of an insulinoma. Serum insulin concentrations taken at the time of hypoglycemia are normal to increased in animals with an insulinoma.
Differential diagnoses for hypoglycemia include:
hypoadrenocorticism
hepatic failure
large extrapancreatic neoplasms
sepsis
polycythemia
insulin overdosage
laboratory error
Treatment of Islet Cell Tumors
Surgery is generally the best option to control clinical signs and improve survival of animals with islet cell tumors, especially in patients with a solitary pancreatic mass.
Although insulinomas are usually solitary in dogs, the entire pancreas should be examined carefully for multiple tumors. Complete excision of the tumor ameliorates the hypoglycemia and associated neurologic signs, unless there have been irreversible changes in the CNS. If there are nonvisible metastases, hypoglycemia may persist after surgery. Even though the potential for malignancy of insulinomas is high, many dogs live >1 yr with acceptable quality of life if all visible tumors are debulked at surgery. Dogs with inoperable tumors may be managed fairly well with multiple feedings per day and glucocorticoid administration (0.5–1 mg/kg/day). Diazoxide (10–60 mg/kg/day, divided into two equal doses) may also alleviate clinical signs in some dogs, although problems with availability have limited its use. Most recommend starting at the low end of the dose range and gradually increasing the dose to effect. The chemotherapeutic agent streptozotocin has been investigated for the treatment of islet cell tumors in dogs and may be considered after surgical resection.
Key Points
Insulinomas are the most common cause of hypoglycemia in older dogs.
Diagnosis is based on documenting inappropriate serum insulin concentrations in the face of hypoglycemia.
Longterm survival is generally < 1 year.
