JJ was a 10 year old, male neutered, Maltese who was diagnosed three months prior with diabetes mellitus. At the time of presentation he was receiving 2.5 units of Caninsulin twice daily. His owners reported good control of symptoms in that he was no longer polyuric, polydipsic or losing weight. He had a good appetite and normal energy levels. The day of presentation was like any other day where in the morning, after eating breakfast, he received 2.5 units insulin but vomited by noon. In the afternoon he was wobbly and shaking. His owners administered 1tbsp of maple syrup. In the evening he ate his dinner and received another 2.5 units of insulin. By midnight he was found to be shaking and unable to get up so they gave him more maple syrup. The following morning he did not receive insulin but ate well. He went to his primary care veterinarian where his blood sugar was noted to be 1.2 mmol/L and he was referred to an emergency and referral hospital.
On presentation his blood glucose was too low to register on the glucometer and he received several boluses of dextrose and 5% dextrose was added to his intravenous fluids. His blood sugar remained consistently under 3mmol/L for the next 72 hours.
A general health profile was performed. His complete blood count was normal but the biochemical profile showed several abnormalities including glucose 0.8 (3.5-6.3mmol/L), Urea 12.3 (3.2-11.0 mmol/L), SDMA 16 (0-14ug/dL), sodium 159 (142-152 mmol/L), chloride 120 (108-119mmol/L), total protein 52 (56-75g/L), ALT 335 (18-121 U/L), AST 145 (16-55U/L), ALP 340 (5-160u/L), Amylase 3509 (337-1469u/L), Lipase 1052 (138-755 U/L), and Spec cPL 1244 (0-200ug/L).
The urine was yellow and clear with a urine specific gravity of 1.031 and pH of 5.0; he had trace protein, and was negative for glucose, ketones, blood, bilirubin, and urobilinogen. Urine microscopy was normal and urine culture, collected by cystocentesis, was negative.
Abdominal ultrasound was performed and the right limb of his pancreas had several ill-defined hypoechoic nodules that measured from 0.23 cm to 0.42 cm.
Chest radiographs were performed and were normal.
A paired insulin:glucose ratio was submitted but results were unavailable prior to discharge.
After 4 days of ICU care his blood sugar increased to >30mmol/L and he was started on a more conservative dose of insulin of 0.5 unit twice daily. At discharge, the owners were instructed to use urine dipsticks to monitor glucosuria and ketonuria at home. With rechecks, his insulin was increased to 1 unit twice daily as his blood sugars remained high and ketones developed in his urine. When we received his insulin:glucose ratio the results were that his insulin was 29.8 (reference 5-40uIU/mL), the glucose was 1.0 (reference 3.3-6.9mmol/L) and the ratio was 216 (reference 14-43). These results are consistent with a diagnosis of an insulinoma.
Insulinomas are malignant neoplasms of the pancreas that produce excessive amounts of insulin resulting in low blood sugar. Common symptoms of an insulinoma include collapse, loss of consciousness, seizures, weakness and other neurological abnormalities. Insulin is released by the tumor periodically and so symptoms are not consistent and frequency is unpredictable. A diagnosis of insulinoma can be made with a paired insulin:glucose ratio when the patient’s blood sugar is low. If the insulin level is inappropriately high for the decreased glucose level, it is suggestive of an insulinoma. Ultrasound, computed tomography, and MRI are other diagnostic tests that may help determine the extent of the pancreatic tumor and assess for metastasis.
Insulinomas are medical emergencies as they can result in seizures, coma and even death. Solitary tumors of a lateral pancreatic limb are ideal for surgical resection. Reported survival times for surgically managed insulinomas varies from 196 to 785 days. Insulinomas that have metastasized are non-surgical and medical therapy would be necessary. Survival times for medically-managed insulinomas have been reported as 74-196 days. JJ was treated medically for his insulinoma because of the multiple pancreatic nodules identified on ultrasound. Given his concurrent diabetes mellitus, surgical resection would have been the obvious choice.
Medical therapy consists of steroids, to stimulate the formation of glucose, and frequent feedings. Other therapies include diazoxide, octreotide, glucagon and chemotherapeutic agents, such as streptozocin. Prednisone was not initiated in JJ because of his pre-existing diabetes mellitus. Instead, he was started on diazoxide (5.2mg/kg orally every 12 hours) to help reduce β cells from secreting insulin. Owners were advised that insulinomas can randomly secrete large amounts of insulin and should this occur they should immediately stop insulin therapy and start feeding small meals every 4 hours. At home, they were able monitor his blood sugars and also use urine dipsticks to guide therapy. When there was glucosuria and blood sugars were high they could safely resume insulin therapy. When there was no glucosuria and blood sugars were low they were to stop insulin administration and administer frequent feedings. This was an exceptionally difficult case to manage, and although exceedingly rare, it has been documented in both human and veterinary medicine. Unfortunately, due to inherent problems associated with managing a diabetic with an insulinoma, JJ was euthanized 1 month after diagnosis.
More commonly, when faced with a hypoglycemic diabetic patient, the clinician should consider errors in the dosing or administration of insulin. Owners should be asked if their pet could have received two doses that morning, clarify the amount that they draw up into the syringe, and should confirm that the appropriate syringe is being used for the type of insulin they are using. Changes in syringe, from U-100 to U-40, can result in hypoglycemia as the dose would be a 2.5X overdose. If no error can be identified with the administration of insulin one should then consider if the patient’s insulin needs have changed or if the patient could be suffering from the Somogyi phenomenon. A blood glucose curve, measuring blood sugars every 2-4 hours, is appropriate to distinguish between the two causes.
Insulinomas in diabetic patient are rare. We are always told that “when you hear hoof beats, think of horses and not zebras”, but this cases makes me think JJ was a unicorn.
This article was submitted by:
Dr. Jennifer Kyes, BSc. DVM, Dip ACVECC
Mississauga Oakville Veterinary Emergency Hospital and Referral Group
2285 Bristol Circle
Oakville, ON L6H 6P8