A TOUGH CASE

Q. Buster is an 11-year-old 75.5-lb neutered male Shar-Pei mix with a sweet disposition. He is receiving carprofen, tramadol, and glucosamine for chronic arthritis. In March, we saw him for a wellness exam, vaccines, and a senior comprehensive profile. At that time, he had elevated alkaline phosphatase (208), amylase (1,242), and lipase (1,313) activities; an elevated cholesterol concentration (431), normal T₄ and free T₄ (by equilibrium dialysis) concentrations; normal complete blood count results; and normal urinalysis results (specific gravity = 1.050, pH = 7, inactive sediment).

We measured the lipase activity again about two weeks later, and it had increased to 5,898. We then recommended an ultrasonographic examination, which identified a small hepatic mass and nodule in the same lobe and left adrenal gland enlargement. The pancreas looked normal, as did the kidneys. The ultrasonographer suspected the increased lipase activity was due to gastrointestinal disease.

About 10 days later, the owners reported a huge and sudden increase in Buster's water intake and urination. A urinalysis revealed glucose (4+), no ketones, a urine specific gravity of 1.042, and pH = 6. His blood glucose concentration that day was 532. We started therapy with Humilin N (Eli Lilly) insulin at 9 U twice a day. The owners bought a home glucose monitoring system, which has seemed to work well.

The problem is that we have continued to increase Buster's insulin dose, and his blood glucose concentration has not budged below 400 at any time during the curve. Most of the time, the owner is getting glucose readings of 400 to 500, and Buster is still experiencing polyuria and polydypsia. He now receives 25 U twice a day.

We have done another urinalysis, which showed no sign of inflammation. But it was a free-catch sample, so a culture has not been done yet. His mouth is in pretty good condition. He eats a holistic diet with brown rice and chicken, which the owners do not want to change because he is sensitive to dietary changes. I am worried about his adrenal gland enlargement and wonder if hyperadrenocorticism could still be possible.

Is it time to consider another insulin, or should I just increase the dose until we reach 1.5 U/kg? Buster has lost 6 lb since his diabetes was diagnosed. Any advice you could give would be appreciated.

A. Some cases are certainly more challenging than others, and this seems to be one of those. First, I would perform a urine bacterial culture since this is the most common cause of insulin resistance. Based on what you have said, I think that Cushing's is unlikely, so I would not explore that further at this point, particularly if the hair shaved from the ultrasonographic scan is growing back. If he has no hair growth, I might think differently because that is a good (and cheap!) marker for an endocrinopathy.

Do you see any response to the insulin? If you see some response but not enough, then I'd keep on increasing the insulin dose. If you don't see any response, I'd make sure that the injection technique was appropriate and that the insulin isn't getting injected into the hair or right through the skin. If there is absolutely no response, you could try giving Buster a dose of regular insulin in the clinic (10 U subcutaneously) and see if his glucose concentration decreases. You'll need to check the blood glucose concentration every 90 minutes for about six hours so that you can see a response. If the concentration does decrease, this would tell me that he is able to respond to insulin, but the NPH is just not doing what we would expect. Therefore, I'd try Vetsulin, starting at 0.25 U/kg twice daily.

The other point I'd like to stress is that the glucose curves must truly involve a reading every two hours. The pattern you are seeing is quite common in patients getting blood glucose checks rather than full curves. In these patients, a rapid drop in the blood glucose concentration is missed and the only value documented is a high blood glucose concentration in response to a low nadir (the Somogyi effect). These patients often receive progressive increases in their insulin dose because of apparent poor response.

If you don't make any progress with these suggestions, I'd perform thoracic radiography to check for occult disease before considering referral to a specialist for a fresh look. An internist may not do any better, but sometimes a new look at a tough case makes a difference. Good luck!

Audrey Cook, BVM&S, MRCVS, DACVIM, DECVIM-CA
Department of Small Animal Clinical Sciences
College of Veterinary Medicine & Biomedical Sciences
Texas A&M University
College Station, TX 77843