Insulinoma

From Dog
Gross appearance of an insulinoma in a dog[1]

Insulinoma is a rare malignant neuroendocrine neoplasia of the β-cells of the canine pancreas[2].

Beta cells comprise 60% to 70% of pancreatic islet cells[3]. Insulinomas have been shown to produce various polypeptides (somatostatin, glucagon, serotonin and pancreatic polypeptide)[4]. Most patients only have clinical signs of hyperinsulinism[5].

Approximately 90% of insulinomas in dogs are malignant and metastasize mainly to the regional lymph nodes, the liver and the omentum[6], causing regional lymphadenopathy.

Insulinomas are commonly diagnosed in middle-aged to old, and large breeds such as Labrador Retrievers and German Shepherds are over-represented.

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[7]. Signs include those related to hypoglycemia (lethargy, seizures and ataxia)[8] and adrenergic effects (tachycardia, tremors, nervousness and polyphagia).

Pre-existing diabetes mellitus is not uncommon[9].

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[10].

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)[11]. Insulin detection usually requires ELISA assaying by a reference laboratory[12].

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[13].

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

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[16], whereas dogs with distant metastasis (stage III) have a median survival time of less than 6 months after surgery[17].

The long-term prognosis after surgical resection of canine insulinoma is poor due to re-occurrence[18] Histological staging and tumor size are good indices for expectant survival time[19][20].

References

  1. Vet Med
  2. Madarame H et al (2009) Retrospective study of canine insulinomas: eight cases (2005-2008). J Vet Med Sci 71(7):905-911
  3. Lurye JC & Behrend EN (2001) Endocrine tumors. Vet Clin N Amer Sm Anim Pract 31:1083–1110
  4. Elie MS & Zerke CA (1995) Insulinoma in dogs, cats and ferrets. Compend Contin Educ Pract Vet 17:51–58
  5. O’Brien TD et al (1987) Canine pancreatic endocrine tumors: Immunohistochemical analysis of hormone content and amyloid. Vet Pathol 24:308–314
  6. Hawkins, KL et al (1987). Immunocytochemistry of normal pancreatic islets and spontaneous islet cell tumors in dogs. Vet Pathol 24(2):170-179
  7. Capen, CC (2002) Tumors of the pancreatic islet cells. In: Tumors in Domestic Animals, 4th ed. (Meuten,D. J. ed.), Iowa State Press, Ames, Iowa. pp:684–691
  8. Fukazawa K et al (2009) Insulinoma with basal ganglion involvement detected by magnetic resonance imaging in a dog. J Vet Med Sci 71(5):689-692
  9. Bryson ER et al (2007) Insulinoma in a dog with pre-existing insulin-dependent diabetes mellitus. J Am Anim Hosp Assoc 43(1):65-69
  10. Iseri T et al (2007) Dynamic computed tomography of the pancreas in normal dogs and in a dog with pancreatic insulinoma. Vet Radiol Ultrasound 48(4):328-331
  11. Caywood DD et al (1988) Pancreatic insulin-secreting neoplasms: Clinical, diagnostic, and prognostic features in 73 dogs. J Amer Anim Hosp Assoc 24:577–584
  12. Oberg J et al (2011) Validation of a species-optimized enzyme-linked immunosorbent assay for determination of serum concentrations of insulin in dogs. Vet Clin Pathol 40(1):66-73
  13. Caywood DD et al (1987) Pancreatic insulin-secreting neoplasms: Clinical, diagnostic, and prognostic features in 73 dogs. JAAHA 24:577–584
  14. Fenton AC (2003) Pancreatic insulin-secreting neoplasia in a 9-year-old Afghan hound. Can Vet J 44(11):918-920
  15. Robben JH et al (2006) Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma. Res Vet Sci 80(1):25-32
  16. Polton GA et al (2007) Improved survival in a retrospective cohort of 28 dogs with insulinoma. J Small Anim Pract 48(3):151-156
  17. Leifer CE et al (1986) Insulin-secreting tumor: Diagnosis and medical and surgical management in 55 dogs. J Am Vet Med Assoc 188:60–64
  18. Steiner JM & Bruyette DS (1996) Canine insulinoma. Compend Contin Educ Pract Vet 18:13–22
  19. Buishand FO et al (2010) Evaluation of clinico-pathological criteria and the Ki67 index as prognostic indicators in canine insulinoma. Vet J 185(1):62-67
  20. Buishand FO et al (2012) Expression of insulin-like growth factor-1 by canine insulinomas and their metastases. Vet J 191(3):334-340