Insulinoma in 2 guinea pigs (Cavia porcellus)

Abstract

This paper describes an insulinoma in 2 guinea pigs (Cavia porcellus). Both guinea pigs presented with neurologic signs and low blood glucose readings. The neurologic signs resolved with dextrose administration. Insulinoma was confirmed on postmortem examination.

Insulinomas are beta-cell tumors of the pancreas that frequently secrete excessive amounts of insulin. The clinical signs that occur are related to the effect of insulin hormone on blood glucose levels (1). Insulinomas have not previously been reported in guinea pigs. The following is a report of 2 guinea pigs that presented for neurologic signs in which the presence of an insulinoma was confirmed.

Case description

Case 1: A 5-year-old, 1.2 kg, female guinea pig (Cavia porcellus) was presented for the sudden onset of twitching and possible seizures. Physical examination revealed a right sided head tilt and paralysis of the left side of the body. The animal had previously been diagnosed with bilateral ovarian cysts and mammary fibroadenomas. She was currently receiving cisapride (compounded, The Veterinary Pharmacy, Guelph, Ontario) and trimethoprim-sulfamethoxazole (Novo-trimel; Novopharm, Toronto, Ontario) for the treatment of diarrhea. She had received 100 μg of leuprolide acetate (compounded, The Veterinary Pharmacy, Guelph, Ontario) 2 d prior to the onset of neurologic signs. Blood analysis (Vettest machine; Idexx, Westbrook, Maine, USA) done 3 mo prior to this presentation had recorded a blood glucose level 4.69 mmol/L, in the low normal range.

A drop of blood from the lateral saphenous vein gave a glucose reading of 0.67 mmol/L on a glucometer (Accu-chek Advantage; Boehringer Mannheim, Laval, Quebec). The guinea pig was given approximately 1.0 mL of 25% dextrose, PO, upon which there was an immediate resolution of the neurologic signs. All medications, except dextrose, were discontinued. The owner administered 25% dextrose, PO, as required to relieve symptoms but elected to have the animal euthanized the next day, as ataxia, twitching, and neurologic signs continued to recur every few hours.

On necropsy, a 3-mm red mass was identified in the pancreas. In addition, there was a mass in the right ovary and a cyst on the left ovary; subjectively, both adrenal glands were enlarged and the liver was pale and friable. Histopathologic examination revealed moderate vacuolation of the hepatocytes, mostly with crisp, clear vacuoles, typical of lipid. The adrenal glands had irregular cortical outlines, with a series of hyperplastic nodules. The spleen had extensive extramedullary hematopoiesis and the ovarian tissue contained a series of serosal cysts, some populated by a papillary proliferation of well-differentiated columnar epithelial cells. The findings in the pancreas consisted of atrophy of pancreatic exocrine tissue and extensive replacement by mature lipocytes, which is a common aging change in this species. In addition, however, there was a massive proliferation of the endocrine tissue. The endocrine tissue occupied 70% of the sample of pancreas submitted for histologic evaluation. The cells were nondescript cuboidal epithelial cells with fairly abundant, finely vacuolated, gray cytoplasm, occasional 3-fold anisokaryosis, and widespread hyperchromasia. The cells did not form tubules but were routinely arranged in small solid packets defined by a delicate fibrovascular stroma. This type of packeting is shared by many of the endocrine neoplasms. On the basis of histologic appearance, anatomic location, and associated clinical signs, the mass was diagnosed as an insulinoma.

Case 2: A 5-year-old, 1.05 kg, intact female guinea pig presented with the sudden onset of ataxia and head tilt. There was a prior history of bilateral mammary fibroadenomas. The findings on physical examination consisted of intermittent severe tonic clonic seizures. In between seizures, the animal showed marked ataxia and profound weakness. Menace reflexes were absent bilaterally, as was the direct pupillary light reflex in the right eye. The animal was presumed blind. A 1- to 2-cm diameter mass was palpated in the cranial ventral part of the abdomen. Blood was obtained from the saphenous vein and a reading of “low” was obtained on the glucometer (Accu-chek Advantage; Boehringer-Mannheim). Dextrose (25%) was administered, PO, and there was a rapid response. Mentation, movement, and reflexes were normal within 15 min. The possibility of an insulinoma was discussed with the owner, who elected euthanasia. The animal was anesthetized with 5% isoflurane by mask; prior to euthanasia, cardiac puncture was used to obtain blood for glucose and insulin measurements. Blood glucose reading at this time was 4.6 mmol/L. Insulin readings (Vita-tech, Markham, Ontario) were reported as less than 3 μg/L. Unfortunately, it was determined later there had been a 4-day courier delay in the sample arriving at the laboratory. It was expected that the serum would not have remained frozen during that time.

On necropsy, a 1-cm red mass was present within the pancreas. There were no other gross pathologic lesions present. Histopathologic examination revealed widespread but subtle insterstitial renal fibrosis with some random radial scars, in which almost all the tubular tissue was lost. These could represent old infarcts or tracts of pyelonephritis, from which the leukocytes had since disappeared and which were unlikely to have been of clinical significance, as there was also a large amount of relatively normal kidney present. The large pancreatic mass consisted of slightly pleomorphic cuboidal epithelial cells arranged in packets of 10 to 20 cells by a delicate fibrovascular stroma. The cells had abundant vacuolated basophilic cytoplasm and a central nucleus. There was generally less than a 2-fold anisokaryosis, but there was occasional mononuclear gigantism.

Mitotic figures were not seen. The histologic appearance, considered in light of the reported clinical signs and response to treatment, was typical of insulinoma.

Discussion

The author could find no reports of insulinomas occurring spontaneously in the guinea pig. The true frequency of this neoplasm in this species is likely unknown. There is unlikely to be an association with ovarian cysts or mammary fibroadenomas, as both of these neoplasms are extremely common in mature guinea pigs (2,3). Although both of these cases were female, it is unknown if there is a sex predisposition. It is also unknown if these 2 guinea pigs were related. Both were obtained locally and were similar in breed and appearance.

Solid-phase radioimmunoassay (Coat-a-count; DPC GmbH, Bad Nauheim, Germany) was used to measure the insulin level. The specific test information is proprietary. Radio-immunoassay tests for insulin have been validated for the canine, bovine, and equine species (4), but not for guinea pigs. Also, the delay in transport could have resulted in degradation of the insulin. Insulin should be frozen and shipped on ice, as it may denature at elevated temperatures. Further research is required to validate the test in this species and allow interpretation of results.

Insulinomas are a fairly common tumor in the ferret (1,5) and have been reported in dogs (6). Diagnosis is frequently suspected on the basis of clinical signs, fasting hypoglycemia, and reversal of the signs with dextrose or feeding (1) and on the results of an insulin/glucose, glucose/insulin, or amended insulin/glucose ratio. Definitive diagnosis may also require histopathologic examination of the tumor (1,5,6). Suggested treatments include surgical removal of the tumor, medical therapy consisting of frequent high protein, low carbohydrate meals, restricted exercise, and drug therapy with medications such as prednisone or diazoxide (1,5,6), or both. Medical therapy has controlled symptoms for periods of 6 mo to 1.5 y in ferrets (1,5) and 12 to 14 mo in dogs (6). Therapy was not attempted in the 2 cases presented here. Surgery to debulk the mass or therapy with prednisone may have been beneficial.

Guinea pigs normally eat throughout the day and generally should have hay available at all times. It would be difficult to otherwise control the frequency of feeding. Treatment of acute hypoglycemic episodes with IV dextrose can result in rebound hypoglycemia due to stimulation of the tumor (5). In case 1, the signs recurred regularly after oral treatment with dextrose. Rebound hypoglycemia may have been a factor.

In conclusion, insulinoma should be considered as a differential diagnosis in mature guinea pigs presenting with a neurologic disorder. Documentation of low glucose levels and response to therapy with dextrose can be useful in confirming the diagnosis. Normal insulin levels have not been reported in guinea pigs and the radioimmunoassay test must be validated in this species. Exploratory surgery to remove or debulk the mass, medical therapy with prednisone, or both, may be reasonable alternatives to euthanasia. CVJ

Figure 1.

Insulinoma. Packets of cuboidal cells with 2-fold anisokaryosis compressing adjacent acini of the exocrine pancreas. The tumor cells are arranged in small solid packets by a fine fibrovascular stroma, a pattern typical of endocrine neoplasms.