Q & A: Hypoglycemia in a 7-Year-Old Laborador Retreiver

I'm writing about a 7-year-old lab that present today for signs associated with hypoglycemia.He has been progressive lethargic for the last week. The owner noted staggering and weakness and brought him into our clinic for evaluation yesterday.

On examination, the dog was quiet but clinically normal. His blood glucose concentration, however, was low at 26 mg/dl (reference range, 70-125 mg/dl). All other serum chemistry results (including serum sodium and potassium were normal. Radiographs of the chest and abdomen were unremarkable. The owner has been quizzed at length about possible xylitol ingestion, but there is no history of possible ingestion.

We hospitalized the dog for observation and started a 5% dextrose drip overnight. This morning, the blood glucose was still quite low (only 47 mg/dl) after being off dextrose for about an hour. I continued the glucose drip (raised it to a 10% drip), and the blood glucose concentrations ranged from 41 to 70 mg/dl throughout the day. He is eating well and alert on the IV glucose supplementation.

My rule outs are the following intoxications or medical disorders:

• Xylitol ingestion 
• Atypical Addison's (the serum electrolytes and Na:K ratio were normal)
• Insulinoma (insulin-secreting pancreatic islet cell tumor)
• Portosystemic shunt

I have submitted an serum insulin level at the time when the dog's blood glucose was very low (42 mg/dl) and the results are still pending. I've also submitted a baseline cortisol concentration to help rule out Addison's disease. I have not measured his serum bile acids because I did not want to fast him just yet.

Any other thoughts, suggestions for diagnostics? Anything I am missing?

My Response:

You have the correct list of differential diagnoses and are working your way through the list properly. I'd agree with not fasting the dog — I'd just do a random bile acid measurement to first see it that's abnormal.

If this dog has an insulinoma, we have to remember that IV administration of dextrose may stimulate secretion by the pancreatic tumor. Insulin release post-hyperglycemia often results in rebound hypoglycemia, which necessitates additional dextrose administration and leads the clinician into a cyclical hyperglycemia/hypoglycemia "chase" which can be difficult to terminate.

In this cases, it an be really helpful to just use glucagon instead. Glucagon for injection (1 mg vial) is reconstituted according to the manufacturer's instructions with supplied diluent, then added to 1000 ml of 0.9% NaCl. The 1000 ng/ml solution is administered intravenously as a constant rate infusion (CRI) with the use of a syringe infusion pump. The glucagon CRI is initially given as a bolus of 50 ng/kg, then administered at a rate of 10 to 15 ng/kg/min. The dose may need to be increased up to 40 ng/kg/min as needed to maintain euglycemia.

Additional Followup:

I've put the dog on a glucagon constant rate infusion and it's been working great to maintain the blood glucose concentration in the normal range in the hospital!

The dog's resting serum cortisol concentration was normal at 3.2 μg/dl, so Addison's disease appears highly unlikely. My serum insulin and bile acid results still pending.

The owner has been internet investigating and he told me that his dog has eaten a birch limb/stick last week. I read that xylitol is derived from hardwoods such as birch — Is there any way the xylan from the birch could be metabolized to xylitol in the dog?

My Response:

You're right, the normal serum cortisol (>2.0 μg/dl) rules out Addison's disease.

As far as xylitol toxicity is concerned, I did some research myself and found that birch wood itself doesn't contain xylitol so that's unlikely to be the cause of the hypoglycemia. And this would be especially true since it was consumed a week ago, and you wouldn't expect continued hypoglycemia if the problem was due to xylitol toxicity.

Outcome:

Abdominal ultrasound showing
multiple hypoechoic masses in liver

The dog's serum insulin concentration, collected at the time of severe hypoglycemia, was extremely high (402 pmol/L; reference range, 60-230 pmol/L). The bile acids values were normal. An abdominal ultrasound revealed a pancreatic mass with several hypoechoic areas in liver, consistent with pancreatic neoplasia with metastasis to the liver. A trial of diazoxide was performed at home, but hypoglycemia persisted.

Based on the poor prognosis and lack of response to diazoxide, the owners elected euthanasia. Multiple pancreatic and hepatic nodules were identified at necropsy; histopathology confirmed beta cell islet cell neoplasia with metastasis to the liver.

Final Diagnosis: Insulinoma (insulin-secreting carcinoma of pancreas), producing hypoglycemia.

References:

1. Dunayer EK. Hypoglycemia following canine ingestion of xylitol-containing gum. Veterinary and Human Toxicology 2004;46:87-88.
2. Leifer CE, Peterson ME, Matus RE. Insulin-secreting tumor: diagnosis and medical and surgical management in 55 dogs. Journal of the American Veterinary Medical Association 1986;188:60-64.
3. Smith SA. Miscellaneous Endocrine Disorders. In Morgan RH, Bright, R, and Swartout MS (eds). Handbook of Small Animal Practice, Fourth Edition. W. B. Saunders, Philadelphia, PA. 2003:731-751.
4. Fischer JR, Smith SA, Harkin, KR. Glucagon constant rate infusion: a novel strategy for the management of hyperinsulinemic-hypoglycemic crisis in the dog. Journal of the American Animal Hospital Association 2000; 36:27-32.
5. Lennon EM, Boyle TE, Hutchins RG, et al: Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005). 
   Journal of the American Veterinary Medical Association 2007;231:413-16.