Q & A: Addison's Disease in a Cat with Juvenile Diabetes

I have a 2-year old, male-neutered DSH cat who had had diabetes mellitus since 4 months of age. He has been very difficult to regulate, but his diabetic regulation and glucose control is much better since changing to ProZinc^®  insulin (Boehringer Ingelheim).

In the past, he has developed recurrent episodes of diabetic ketoacidosis. During each of these episodes, the cat had hyponatremia and hypochloremia. Because of these serum electrolyte changes and the fact that we are having trouble getting him to gain weight, I thought that Addison's disease should be ruled out.

I ran a baseline cortisol concentration 1 week ago, and the value was low at 0.7 μg/dl (reference range, 1.0-4.0 μg/dl). I did an ACTH stimulation test this week to rule out Addison's disease. For this test, I used cosyntropin (Cortrosyn^®) and administered a whole vial (0.25 mg or 250 μg), IV. The results of cortisol results before and after ACTH administration are as follows:

• 0 min (Pre-ACTH): 2.4 μg/dl (reference range, 1.0-4.0 μg/dl)
• 30 min (Post-ACTH): 5.3 μg/dl (reference range, 5.0-12.5 μg/dl)
• 60 min (Post-ACTH): 4.4 μg/dl (reference range, 5.0-12.5 μg/dl)

As you can see, the basal cortisol value is now completely within normal range, but both ACTH-stimulated cortisol values are low-normal. I don't understand why the baseline cortisol was so low 2 weeks ago but now it's so normal. But the response to ACTH stimulation still appears blunted.

Did I do the test correctly? Does this cat have Addison's disease or not?

My Response:

Both cortisol and ACTH are secreted in pulses throughout the day (episodic secretion) with peaks and valleys in hormone levels (1). So it would be very possible to take two serum samples for cortisol measurement just separated by just a few minutes and obtain two very different cortisol values. In my experience, cats tend to have lower basal cortisol concentrations than dogs, so the value of 0.7 μg/dl may be "normal," at least for this cat.

As far as this cat's blunted cortisol response to the cosyntropin (Cortrosyn^®)  injection, cats do not always respond as well as dogs (2,3), so I would consider this cat's ACTH stimulation test to be normal. Again, the post-ACTH peak serum cortisol concentrations tend to be lower in normal cats than the cortisol response seen in dogs. Because an low-normal cortisol response in a cat could be interpreted as severely blunted if the canine reference range is used, it is important for each laboratory to establish their own reference range values for cats. Obviously not all labs have actually done the work necessary to properly establish their own reference range values for all hormones, especially in the cat.

The bottom line: These results completely rule out Addison's disease.

Your protocol for performing the ACTH stimulation test in this cat is fine and certainly provided maximal adrenocortical stimulation, which is the goal of the ACTH stimulation test. Cosyntropin is the preferred ACTH preparation in cats, as it is in dogs. But let's talk more the best protocol for performing this test in cats, because there are some major differences between ACTH test protocols in cats and dogs.

First of all, the route of administration is very important in cats. In dogs, cosyntropin can be administered either IV or IM, with an equivalent cortisol response. In contrast, Cortrosyn should be administered IV to cats, because the adrenocortical response is more consistent and the peak cortisol is higher when given by that route. Given intramuscularly, the cosyntropin is not well absorbed in cats. In addition, giving cosyntropin by the IM route is painful for cats and therefore should be avoided.

Traditionally, it has been recommended that we collect post-ACTH cortisol samples at 30 and 60 minutes in cats to ensure detection of the peak cortisol response (4). However, this was based on the use of the intramuscular route of administration, where the peak cortisol response is lower and occurs earlier, generally at 30 minutes (4). By using the IV route of administration, the peak cortisol response in cats, as well as dogs, occur by 60 to 75 minutes after injection, so a sampling time of 60 minutes is recommended (2,3,5).

For many years, we have recommended administration of a relatively large dose of cosyntropin (125 μg per cat) to ensure an adequate and prolonged adrenocortical response in cats. However, it is clear that this 125-µg dose of cosyntropin, at least when administered IV, exceeds that needed to induce maximal adrenocortical stimulation in clinically normal cats, and that smaller doses can maximally stimulate the adrenal cortex (3,5).

A recent report evaluated the lowest feline dose of cosyntropin, based on body weight, that produced maximal cortisol secretion equivalent to that achieved with the standard dose of 125 μg per cat (5). In that study, the lowest cosyntropin dose that resulted in maximal cortisol response was 5 μg/kg and occurred at 60 to 75 minutes after IV cosyntropin administration. This 5 μg/kg cosyntropin dose is identical to that generally used in dogs for ACTH stimulation testing.

The bottom line: Low-dose ACTH stimulation testing with 5 μg/kg cosyntropin given IV followed by blood sample collection at 60 minutes in cats produced results equivalent to those produced by the traditional 125 μg per cat dose.

Lastly, let me comment about this cat's diabetes. Juvenile diabetes is extremely rare in cats (6,7). Most of these cats appear to have hypoplasia of the pancreatic islets, so almost all are life-long diabetics. Typically, cats and dogs with juvenile diabetes mellitus are extremely brittle, prone to ketoacidosis, and difficult to regulate. Therefore, I'm very pleased to learn that this diabetic cat is doing so well on the twice daily ProZinc insulin.

References:

1. Kemppainen RJ, Peterson ME. Domestic cats show episodic variation in plasma concentrations of adrenocorticotropin, alpha-melanocyte-stimulating hormone (alpha-MSH), cortisol and thyroxine with circadian variation in plasma alpha-MSH concentrations. European Journal of Endocrinology 1996;134:602-609.
2. Peterson ME, Kemppainen RJ: Comparison of intravenous and intramuscular routes of administering cosyntropin for corticotropin stimulation testing in cats. American Journal of Veterinary Research 53:1392-1395, 1992.
3. Peterson ME, Kemppainen RJ: Dose-response relation between plasma concentrations of corticotropin and cortisol after administration of incremental doses of cosyntropin for corticotropin stimulation testing in cats. American Journal of Veterinary Research 54:300-304, 1993.
4. Smith MC, Feldman EC. Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats. American Journal of Veterinary Research 1987;48:1719-1724.
5. DeClue AE, Martin LG, Behrend EN, et al. Cortisol and aldosterone response to various doses of cosyntropin in healthy cats. Journal of the American Veterinary Medical Association 2011;238:176-182.
6. Woods PJ, Panciera DL, Snyder PS, et al. Diabetes mellitus in a kitten. Journal of the American Animal Hospital Association 1994; 30:177-180.
7. Thoresen SI, Bjerkås E, Aleksandersen M, et al. Diabetes mellitus and bilateral cataracts in a kitten. Journal of Feline Medicine and Surgery 2002; 4:115-22.

To see more of my related posts on this topic, click on the links below:

• What ACTH Preparations Should Be Used For Stimulation Testing? 

• What's the Best Protocol for ACTH Stimulation Testing in Dogs and Cats?