Managing Addison's Dogs with Concurrent, Uncontrolled Diabetes

I have a 10-year old male Terrier dog named Scooter who now weighs in at 11 pounds (5 kg). He was originally diagnosed diabetes mellitus that we could not get regulated with Vetsulin, even at doses as high as 8 units twice daily. 

Scooter was subsequently diagnosed with with pituitary-dependent Cushing's disease and was treated with mitotane (Lysodren). Once we got the Cushing's disease under control, his daily insulin requirements fell to 3 units twice a day, and the diabetes was well regulated based on glucose curves done at my vet's hospital. However, after a few months of treatment with mitotane, it was apparent that Scooter had been severely overdosed with the medicine, which resulted in complete adrenal insufficiency and threw him into a severe Addison's crisis. It was a near death experience for him, but he has pulled threw and is now doing much better off of the mitotane and on treatment for his iatrogenic Addison's disease. 

Now we have spent the last 3 months trying to stabilize his iatrogenic Addison's disease and concurrent diabetes. Currently, he is on 2.5 mg of fludrocortisone (Florinef) twice day along with 1.25 mg of prednisone twice daily. The Florinef dose has had to be gradually increased to keep his serum electrolytes (sodium and potassium) within their proper ratio and ranges. Based on his last blood test, we may have to increase it yet again, since his serum potassium remains slightly high. 

To make matters even worse, his diabetes is now completely out of control, as evidenced by his intense thirst and excessive urinations with heavy amount of glucose in the urine. Serial blood glucose monitored done at my veterinarian's clinic confirms that the blood glucose readings remain very high throughout the day. We have gradually increased the insulin dose back up to 7 units twice daily, but it just doesn't seem to be working at all at this point. 

What do you recommend that I do? We need to get the Addison's disease controlled but as we have raised the doses of the Florinef and prednisone, Scooter's diabetes is getting worse! My vet has suggested that I transition Scooter from the Florinef tablets to Percorten injections in order to stabilize his serum electrolytes. He also told me that the Florinef contains some steroid activity which may be contributing to his high insulin doses.  Is the steroid in Florinef any less hard on him than the prednisone?   

Any advice would be greatly appreciated. 

My Response: 

With Scooter, we need to address both his poorly-regulated Addison's disease and his uncontrolled diabetes, as well as the increased thirst (polydipsia) and urination (polyuria). There is a lot going on with Scooter, so let's take one problem at a time.

Mineralocorticoid replacement: Florinef vs. Percorten-V? 
For mineralocorticoid replacement for dogs with Addison's disease, either oral fludrocortisone acetate (Florinef) or injectable desoxycorticosterone pivalate (DOCP; Percorten-V) can be used successfully (1-3).

In your dog, however, I would definitely make the switch to Percorten-V. Some dog's just don't respond very well to treatment with Florinef, and it's not uncommon for dogs to require increasing doses of daily Florinef over time to control the serum electrolyte concentrations (1-3). With high doses of Florinef, this can lead to signs of increased thirst and urination, and may also lead to problems with management of diabetes, as you are seeing in Scooter.

Since you are having problems controlling the serum electrolytes, I'd recommend starting with the label dose of 2.2 mg/kg, injected every 25-30 days (4). If this drug works to stabilize the serum sodium and potassium levels (and I expect that it will), then we can try to gradually lower the Percorten dosage after a few weeks to months (e.g., I generally try reducing the dose by 10% or so each month). Many dogs will maintain normal serum electrolyte levels on doses between 1-1.5 mg/kg per month, and a few will even need less (1,5).

Glucocorticoid supplementation in Addison's disease
Now let's next turn to your dog's glucocorticoid needs. Dogs with Addison's disease, either spontaneous or iatrogenic (that is, drug-induced, as it was in Scooter), will require replacement glucocorticoids (e.g., prednisone or prednisolone) in addition to the mineralocorticoid supplementation (1-3). Some dogs will do fine without any glucocorticoid supplementation, but the vast majority of dogs will feel better with a small daily dose of glucocorticoid administered daily. Since we know that these dogs cannot secrete normal amounts of cortisol, it certainly makes a great deal of sense to use low-dose glucocorticoid replacement.

Unfortunately, many dogs with Addison's disease are treated with too much glucocorticoid. Remember that our goal with glucocorticoid supplementation is to provide the same amount of steroid that the dogs would normally produce if their adrenals had not failed.

For dogs, the daily glucocorticoid maintenance dose for prednisone is only 0.1-0.2 mg/kg/day (3), so that calculates out to only 0.5-1.0 mg per day for Scooter, quite a bit lower that what you are currently giving (2.5 mg per day). That would certainly be enough to cause an increased thirst by itself, but would also contribute to glucocorticoid-induced insulin resistance, making the diabetes uncontrollable despite the higher insulin doses.

Therefore, we should try to lower the prednisone dosage first down to 1.0 mg once daily (or divided). If he is doing well clinically (i.e., normal appetite and no vomiting), then the dose can be lowered even further, down to 0.5 mg per day. Prednisone or prednisolone are available in 1-mg tablets, as well as an oral solution, making it possible to administer these smaller dosages (6,7).

Florinef also contains significant glucocorticoid activity
In addition to the fact that Addison's dogs are commonly overdosed with prednisone, it's very important to realize that fludrocortisone acetate also possesses moderate glucocorticoid activity, as well as having marked mineralocorticoid potency (2,3). By comparison, fludrocortisone has 10-times the glucocorticoid activity and 125-times the mineralocorticoid activity of cortisol, the glucocorticoid hormone secreted by the adrenal gland. In this regard, fludrocortisone is very different than Percorten-V, which possess no glucocorticoid activity (2,3).

For the dog with Addison's disease, a glucocorticoid is a glucocorticoid —it makes no difference to Scooter if this glucocorticoid activity comes from prednisone or from the Florinef.  This potent glucocorticoid activity of fludrocortisone explains why some dogs will develop polydipsia and polyuria, common side effects associated with higher-dose glucocorticoid treatment in dogs (8). This is another reason why we need to get Scooter off of the Florinef and switch to the Percorten-V.

Glucocorticoid-induced insulin resistance
In all likelihood, the reason for Scooter's poorly controlled diabetes is related to insulin resistance associated with glucocorticoid excess (9,10). By stopping the Florinef and providing mineralocorticoid replacement with Percorten-V instead, we will remove one source of excess glucocorticoid. Lowering his daily prednisone dose will also help.

As we remove the cause of the insulin resistance, the dose of insulin will again fall. You should monitor Scooter closely during this period to ensure that insulin overdosage and hypoglycemia do not occur, and lower the insulin dose as needed.

Don't forget to rule out urinary tract infections
Finally, don't forget that diabetic dogs, no matter what the cause, will commonly develop urinary tract infections. Think about it: a bladder full of sugar-laden urine is a perfect breeding ground for bacteria to thrive! Such urinary tract infections will also commonly contribute to insulin resistance (9,10) but can also lead to kidney failure, if the infection ascends from the bladder up to the kidneys.

For this reason, I always recommend checking a complete urinalysis and urine culture in all dogs (and cats) with insulin resistance. However, even if the diabetes is well-controlled, I still recommend doing a urinalysis with culture twice yearly in all of my diabetic patients.

References: 

1. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;11:43-49. 
2. Church DB. Canine hypoadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;156-166.
3. Kintzer PP, Peterson ME. Canine hypoadrenocorticism In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2014; pp 233-237.  
4. Lynn RC, Feldman EC, Nelson RW. Efficacy of microcrystalline desoxycorticosterone pivalate for treatment of hypoadrenocorticism in dogs. DOCP Clinical Study Group. J Am Vet Med Assoc 1993;202:392-396. 
5. Bates JA, Shott S, Schall WD. Lower initial dose desoxycorticosterone pivalate for treatment of canine primary hypoadrenocorticism. Aust Vet J 2013;91:77-82. 
6. Peterson ME: Treating small-breed Addison's dogs with low doses of prednisone or prednisolone. Animal Endocrine Clinic blog, December 14, 2013. 
7. Plumb, DC. Plumb's Veterinary Drug Handbook. Seventh Edition, Wiley-Blackwell. 2011.
8. Melián C, M. Pérez-Alenza, D, Peterson ME. Hyperadrenocorticism in dogs, In: Ettinger SJ (ed): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Seventh Edition). Philadelphia, Saunders Elsevier, 2010;1816-1840.
9. Hess RS. Insulin resistance in dogs. Vet Clin North Am Small Anim Pract 2010;40:309-316. 
10. Peterson ME. Diagnosis and management of insulin resistance in dogs and cats with diabetes mellitus. Vet Clin North Am Small Anim Pract 1995;25:691-713.  

Tapering the Glucocorticoid Dose in Dogs with Addison's Disease

My dog is a 2-year old, male Saint Bernard., weighing almost 145 pounds (75 kg). He was just diagnosed with Addison's disease and was treated with an intramuscular injection of Percorten-V (65 mg) and started on oral prednisone (30 mg per day —15 mg in AM and 15 mg in PM). 

As my veterinarian and I are learning more about treating Addison's disease in dogs, we realize that he is now suffering from cortisol overload. His current signs include lethargy, frequent urinations and incontinence, and excessive hunger and thirst. 

After reading your work, we know that we should lower his daily prednisone dose, probably down to 5 mg per day. Considering that he hasn't been on it for even a week, I've started to taper the dose fairly rapidly. His appetite remains fine but he now has some diarrhea. 

Here is how we've begun lowering the daily prednisone dosage: 

• Day 1-4: 15 mg twice a day (AM and PM)
• Day 5-6: 15 mg in AM, none at night 
• Day 7: 10 mg in AM, none at night  

Can I just give him 10 mg today and begin just 5 mg tomorrow? Or is that too much danger without tapering? 

My Response: 

You should be fine to lower the dose to 5 mg per day now. Remember that a 5-mg dose is the human replacement dose, so we are still giving the amount that you or I would need to survive. So even for your large breed dog, that will still be plenty!

As far as how fast to taper, you can base that on his appetite. As long as he is eating well without vomiting, you should be fine to taper the dose down, especially since he has also received the mineralocorticoid supplementation (i..e, Percoten-V).

You might want to check his serum chemistry panel and electrolytes soon, just to ensure that the serum sodium and potassium are back within the reference range limits.

Follow-up Question: 

I have lowered the prednisone dose to 5 mg once daily in the AM, which he has been on for the last week. He seemed fine for the first few days on this new dose (good appetite, no vomiting or diarrhea), but more recently he has been pretty lethargic.  

Could this be because he only gets prednisone once a day? Can I experiment and give a divided dosage, with 2.5 mg in the AM and another 2.5 mg in the PM? 

Follow-up Response: 

Yes, dividing the dose of the prednisone may help and certainly can't hurt.

Remember, however, that dogs with Addison's disease have both glucocorticoid and mineralocorticoid deficiencies. Some of his lethargy could be related to the fact that his mineralocorticoid dosage might need to be adjusted.

Therefore, it's important to have his serum chemistry panel and electrolytes rechecked. After the first injection of the Percorten-V, I recommend rechecking the serum electrolytes at 10-14 days and then again at 25-30 days, just before the second injection.

References:

1. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;11:43-49. 
2. Church DB. Canine hypoadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;156-166.

Working Up the Asymptomatic Dog for Cushing's Disease

I have an 11-year old small (20 pounds) male dog of mixed breeding. In preparation for a routine dental procedure, he had a blood panel done, which showed that two of his liver enzymes are high. The serum alkaline phosphatase was 617 U/L (normal < 100 U/L), and the serum alanine aminotransferase (ALT) was 172 U/L (normal < 100 U/L).

He was placed on Denosyl (SAMe) at the daily dosage of 90 mg for 6 weeks. Repeat serum chemistry testing at that time revealed that his liver enzyme levels were slightly decreased, with an alkaline phosphatase value of 426 U/L and an ALT of 115 U/L.

My vet then changed his medication to Denamarin (a supplement containing both SAMe and milk thistle) and suggested retesting in 4 weeks.  When I brought my dog in for that recheck, however, the vet did an ACTH stimulation test instead of running the liver enzymes! The results of the ACTH stimulation test were normal, with a baseline cortisol value of  2.1 µg/dL and a post-ACTH cortisol value of 14.1 µg/dL. Despite the fact that both of those cortisol levels are within the normal range, the vet is now telling us he thinks our dog has Cushing's disease and wants to do an ultrasound at a cost of $300!

My dog is COMPLETELY asymptomatic, and he has no signs of Cushing's disease (normal thirst, appetite, and hair coat). I would have never known he had high liver enzymes without the dental blood panel. Now I feel like I'm being taken for a ride. He has not been rechecked for liver enzymes so I have no idea if the medication he's been on has been working, and we're chasing this test result that by the vet's own admission can be greatly skewed by stress. Finally, he still needs the dental!

Am I wrong for declining the ultrasound and seeking a second opinion or am I missing something here? What would your recommend?

My Response:

What you're describing in your dog is a common scenario that we see frequently in every day practice. The increases in the liver function tests that are present in your dog could indeed be due to Cushing's syndrome, which is a common disease in older dogs (1). Dogs with Cushing's disease tend to develop a characteristic type of hepatopathy, which frequently helps lead us to the diagnosis (1-3). However, the liver enzymes may be high because of primary liver disease too (2).

The Denosyl and Denamarin can't hurt your dog and may help some types of liver disease, but they probably aren't going to change the clinical course if he does have Cushing's disease.

Testing for Cushing's disease
The finding of normal results on an ACTH stimulation test certainly goes against the diagnosis of Cushing's disease. However, the finding of normal results would not be all that unusual in a dog with early or mild Cushing's disease. For that reason, the ACTH stimulation test is not my test of choice for screening dogs with possible Cushing's syndrome. I'd rather do a low-dose dexamethasone suppression test, which is a more specific test since it evaluates the entire pituitary-adrenal axis (1,4-6).  But that's an 8-hour test and more money, so you might want to either just continue to monitor the liver tests or go straight to an abdominal ultrasound at this point.

Why do an abdominal ultrasound in this dog?
In my opinion, performing an abdominal ultrasound this time is not a bad idea. Doing an ultrasound examine would allow us to take a good look at the liver to determine if the liver is small or large in size, as well as to look for any obvious pathology (e.g., liver nodules or tumors). Dogs with Cushing's disease tend to develop liver changes that have a characteristic appearance on ultrasound, so that can also help us in the diagnosis (1,7).

In addition to just examining the liver, performing an ultrasound examination will also allow us to look at the entire abdomen, including the adrenal glands. If both adrenal glands are large, that can be consistent with pituitary-dependent Cushing's disease, the most common type of this disease in dogs. On the other hand, if one adrenal gland is very large and the other is very small, that would be consistent with unilateral adrenal tumor (1,3,8). Since half of adrenal tumors are malignant (1), it's always a good idea to locate the adrenal tumor and remove it as soon as possible.

Now most likely, your dog does not have an adrenal tumor, and he may not have Cushing's disease at all. If both adrenals are enlarged (consistent with pituitary-dependent Cushing's disease),  I certainly wouldn't start treatment immediately since your dog is not showing any clinical signs.  None of the medical treatments we use for Cushing's disease, including trilostane (Vetoryl) or mitotane (Lysodren) actually cure the dog — these drugs only act to lower the cortisol values and control the clinical signs (1).  Again, if you dog has an adrenal tumor, I'd recommend removing it because of the risk of malignancy.

If your dog does have mild Cushing's disease, it is likely that clinical signs will develop at some time in the future. This could be in a week or a year or more, and may never happen.

What about the dental procedure?
If the abdominal ultrasound rules out significant liver pathology (i.e., no hepatic tumors or cancer) and both adrenal gland are similar in size (i.e., no adrenal tumor), then I would definitely recommend having the dental procedure done. Some dogs with severe dental disease can develop high liver enzymes secondary to the oral inflammation, so a good dental procedure may actually help to lower the liver function tests.

References:

1. Pérez-Alenza D, Peterson ME. Hyperadrenocorticism in dogs In: Ettinger SJ,Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Seventh Edition) Philadelphia, Saunders Elsevier, pp 1816-1840, 2010. 
2. Sepesy LM, Center SA, Randolph JF, et al. Vacuolar hepatopathy in dogs: 336 cases (1993-2005). J Am Vet Med Assoc 2006;229:246-252. http://www.ncbi.nlm.nih.gov/pubmed/16842046 
3. Graves TK. When normal is abnormal: keys to laboratory diagnosis of hidden endocrine disease. Top Companion Anim Med 2011;26:45-51. 
4. Peterson ME. Diagnosis of hyperadrenocorticism in dogs. Clin Tech Small Anim Pract 2007;22:2-11.
5. Gilor C, Graves TK. Interpretation of laboratory tests for canine Cushing's syndrome. Top Companion Anim Med 2011;26:98-108 
6. Kooistra HS, Galac S. Recent advances in the diagnosis of Cushing's syndrome in dogs. Vet Clin North Am Small Anim Pract 2010;40:259-267. Melián CM, 
7. Hoffmann KL. Ultrasonographical examination in canine hyperadrenocorticism. Aust Vet J 2003;81:27-30. 

How to Adjust the Glucocorticoid Dose in Dogs Treated for Addison's Disease

Zoe, a female Rat Terrior with Addison's disease

Zoe is a 4-year-old 17.5 lb (8.0 kg) female Rat Terrier who was diagnosed with Addison’s disease 7 months ago. She receives Percorten injections every 28 days, along with 5 mg of prednisone daily.

She is active and playful but is always famished. Her water intake has also increased on the medication, but she isn't showing any incontinence.

My major concern is that she has lost her hair on all four legs and belly, and now it is progressing up her shoulders, hind quarters, and to her head!

Her lab tests are within normal range according to her vet, who wants to take a wait and see approach. I thought she may be getting too much prednisone, but my vet is afraid to cut back for fear of her ”crashing” and developing an adrenal crisis.

Any thoughts on this? Zoe could sure use the help before all the other dogs start teasing her!

My Response:

Based on the clinical features of increased appetite, increased thirst, and hair loss, it is most likely that Zoe is being overdosed with the prednisone and has developed iatrogenic Cushing's syndrome (glucocorticoid excess).

In support of that, the daily maintenance dose of prednisone or prednisolone in dogs with Addison's disease is only 0.1-0.2 mg per kg per day. So at 8 kg (Zoe's body weight), that calculates out to 0.8 mg to 1.6 mg per day. This is only 15-30% of the dose that she is now receiving every day. When you think about that, it's no wonder that she is showing signs of glucocorticoid (prednisone) excess!

Remember that the adrenal glands in dogs with Addison's disease have failed so we must replace the missing hormones. These dogs will require lifelong replacement with both a mineralocorticoid (e.g., Percoten-V) and glucocorticoid (e.g., prednisone) hormone.  Both the mineralocorticoids and glucocorticoid dosages must be individualized for that particular dog.

The dosage of the mineralocorticoids can best be determined by monitoring the serum electrolyte concentrations (sodium, chloride, and potassium); the dosage is increased to decreased, as needed to normalize the circulating electrolyte concentrations.

Prednisone (or prednisolone), a common glucocorticoid used to treat dogs with Addison's disease, is ideally started at physiological dosages (0.1-0.2 mg/kg/day). This dosage should be adjusted up or down as needed, as some dogs show exquisite sensitivity to the adverse prednisone’s effects. The amount of prednisone that enhances the dog’s well-being (normal activity level and appetite) but prevents side effects (increased thirst, panting, polyphagia, hair loss) may be very small.

If a dog's serum electrolytes are normal on Percorten replacement therapy, dogs with Addison's disease aren't going to develop serious adrenal crisis, even if the prednisone dosage is lowered too much for a day or two.

My Bottom Line: 

Your dog is receiving too much glucocorticoid supplementation. With time, even a mild overdose will lead to signs of iatrogenic Cushing's syndrome, which may include hair loss, increased thirst and urination, and increased appetite. I'd taper the dose down to 1 mg per day over the next couple of weeks. The prednisone is available as a 1-mg tablet, which would make dosing much more convenient.

If the hair loss doesn't resolve after two to three months, I'd recommend that your veterinarian check a serum thyroid panel. Some dog's with Addison's disease will also develop concurrent hypothyroidism, which commonly leads to hair loss in dogs.

References:

1. Church DB. Canine hypoadrenocorticism. In: Mooney CT, Peterson ME, eds. BSAVA  Manual of Canine and Feline Endocrinology. 3rd ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2004; 172-180.
2. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;11:43-49.
3. Klein SC, Peterson ME. Canine hypoadrenocorticism: part I. Can Vet J 2010;51:63-69.
4. Klein SC, Peterson ME. Canine hypoadrenocorticism: part II. Can Vet J 2010;51:179-184.

Air Travel with a Dog with Addison’s Disease

I have a 10-year old, 25 kg, female lab who was diagnosed with Addison’s disease about 5 years ago. She has been well-controlled on oral Florinef (0.3 mg, twice daily) and prednisone (2.5 mg, once daily).

I am moving from Canada (Nova Scotia) to Europe and do not want to leave her behind, if it is at all possible.  Do you think that I could fly her to Europe with me or that is not an option?

 I'll do whatever you recommend and feel is best for my dog!

My Response: 

As you have proven in your dog, primary hypoadrenocorticism (Addison's disease) is a readily treatable disease with an excellent prognosis, provided that proper monitoring and treat­ment is maintained for life. Dogs on adequate maintenance therapy should expect to lead rela­tively healthy lives, with no obvious impairment to exercise or other usual activities (1,2).

Therefore, if your dog's Addison's disease is well-controlled, flying should not be a problem. Before you go, I'd repeat a serum chemistry profile, which should include tests for kidney function (urea nitrogen and creatinine) as well as serum electrolytes (sodium, potassium). We want to make sure that her Addison's disease is perfectly regulated the day she leaves for her new home in Europe.

However, it is vitally important remember that these dogs have no adrenocortical reserve and cannot secrete additional cortisol in times of stress, like normal animals would be expected to do. Therefore, any non­adrenal illness or stressful event (such as air travel) needs to be matched with an appropriate increase in the amount of gluco­corticoid administered.

So what does that mean in practical terms for your dog? Because of the stress of the air travel, however, I would recommend that you increase the glucocorticoid supplementation (i.e., the prednisone) on the day that you travel. You are giving a relatively low maintenance dose of prednisone now (0.1 mg/kg/day). I'd recommend that you double this daily dose on the day you travel and continue the higher dose (as needed) for 2-3 days once you arrive.

References:

1. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;11:43-49. 
2. Church DB. Canine hypoadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;156-166.

Managing Urinary Incontinence in Dogs Treated for Addison's Disease

I am the owner of Abbie, a 55 pound (25 kg) female spayed dog with Addison’s disease. She was diagnosed in January of this year; Abbie has been treated with daily prednisone (1.5 mg/day), as well as an intramuscular injection of Desoxycorticosterone pivalate (DOCP; Percorten-V, Novartis) given every 3 weeks (1.8 mg/kg).

All of Abbie's clinical signs have resolved but our problem is that she now has an ongoing issue with urinary incontinence. I just do not know whether this is due to too much or not enough prednisone or DOCP. We have tried increasing the prednisone dose for a day but it doesn't appear to help. Her routine serum chemistry panel done this week was normal with a sodium:potassium ratio of 35 (serum sodium, 149 mEq/L; serum potassium, 4.2 mEq/L).

This has been a rough ride for Abbie and us. There is not a lot of literature I can find. I would appreciate ANY helpful suggestions you may have.

My Response:

You don't mention if Abbie is drinking and urinating more or if she is only showing urinary incontinence.  Many dogs treated for Addison's disease will develop polyuria and polydipsia (increased thirst and urination) secondary to the drug they receive (1-3). Some of those dogs will develop an overflow incontinence (i.e., the bladder overfills and the dogs will leak urine, especially overnight when they haven't been walked for a few hours).

Why do dogs treated for Addison's disease develop a increased thirst and urination?
In dogs, treatment with any form of glucocorticoid (e.g., prednisone, prednisolone, methyprednisonlone, cortisone, dexamethasone) can lead to a form of nephrogenic diabetes insipidus (3). In simple terms, this means that the kidneys loose the ability to concentrate the urine, and this can result in large volumes of urine being produced.

To avoid this complication, it's very important not to give too much of any of these glucocorticoids — for prednisone or prednisolone, the maintenance dosage to replace the missing glucocorticoid hormones is about 0.1 mg/kg/day (or about 2.5 mg/day in Abbie) (1).  So, for Abbie, her dosage of 1.5 mg per day is not at all high, in fact, you might think that raising it could help — unfortunately, it could make her feel better if she is deficient, but giving more glucocorticoid will never help polyuria or urinary incontinence.

Treatment or control of polyuria, polydipsia or incontinence in dogs treated for Addison's disease
Unfortunately, some dogs (like Abbie) are simply overly sensitive to the "correct" dosages of glucocorticoid which are being given. Management of these dogs can be complicated, but may include one or more of the following steps (3):

1. Stopping all salt supplementation (if the dog is receiving any NaCl supplementation).

2.  Reducing the glucocorticoid dosage or stopping administration completely, if possible. Many dogs will do fine getting prednisone every 2 or 3 days. In some dogs, glucocorticoids can be discontinued without any ill effects and mineralocorticoid replacement alone will adequately control signs of hypoadrenocorticism.

3.  If glucocorticoid is required to prevent signs of hypoadrenocorticism, the glucocorticoid can be switched from prednisone or prednisolone to either cortisone acetate or methyprednisonolone (Medrol).

Cortisone acetate is a synthetic steroid that has equipotent glucocorticoid and mineralocorticoid activity (1,4). Therefore, it will provide more mineralocorticoid activity than other synthetic glucocorticoids, such as prednisone or prednisolone. In addition, its shorter half-life and lower overall activity means it is less likely to create polyuria or polydipsia. Generally, a daily dose of approximately 1.0 mg/kg provides adequate glucocorticoid coverage (1).

Methyprednisonolone (Medrol), the 6-methyl derivative of prednisolone, is also associated with less polyuria than that seen with prednisone or prednisolone (3). The daily maintenance dosage for this glucocorticoid is similar to prednisolone (0.2 mg/kg).

4. If all of the above fails, one can reduce the monthly dosage of DOCP and evaluate the effect.

5. Finally, if on Florinef instead of DOCP, then a switch to Percorten-V may solve the problem (obviously, this is not the case for Abbie).

Urinary incontinence without any increase in thirst
If Abbie's thirst is completely normal, however, it certainly is possible that she has estrogen-responsive incontinence (not uncommon in spayed female dogs) or a urinary tract infection (5,6). If you haven't already done so, I'd recommend that your veterinarian do a complete urinalysis and urine culture. If an infection is found, administration of an appropriate antibiotic may cure the incontinence.

References and Suggested Reading:

1. Church DB. Canine hypoadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;156-166.
2. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;11:43-49.
3. Nichols R, Peterson ME. Investigation of polyuria and polydipsia In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;215-220.
4. Plumbs DC. Plumb's Veterinary Drug Handbook. Seventh edition. Wiley-Blackwell; 2011.
5. Forsee KM, Davis GJ, Mouat EE, et al. Evaluation of the prevalence of urinary incontinence in spayed female dogs: 566 cases (2003-2008). J Am Vet Med Assoc. 2013;242(7):959-962.  
6. Stöcklin-Gautschi NM, Hässig M, Reichler IM, et al. The relationship of urinary incontinence to early spaying in bitches. J Reprod Fertil (Suppl) 2001;57:233-236. 

Interpreting the ACTH Stimulation Test in Dogs with Suspected Addison's Disease

I am hoping you may be able to offer me some insight/information about testing for hypoadrenocorticism (Addison's disease) in dogs.

I have a 3-year old male neutered German Shorthaired Pointer. Since April, Luke has been steadily losing weight despite no changes in his diet. He has also seemed "off" (slightly lethargic, just not himself) and had slight changes in gait from time to time. He then would seem better and back to his normal self.

In November, he began having chronic diarrhea and losing weight at a much more rapid pace. He has now last 20 pounds, going down from 85 to 65 lbs. He has had an ultrasound, exocrine pancreatic insufficiency test, full tick panel, fecal tests, serum thyroid tests, and complete blood count and serum chemistry panel. No clinically significant abnormalities have been detected in any these tests.

He had no response to treatment with Panacur, Proviable, or Flagyl. He responded to high-dose prednisone, but then when we tapered the dose, his clinical signs returned. He was off prednisone for 3 days before doing the first ACTH stimulation test, which came back out of range:

• Basal cortisol: 1.2 μg/dl (Reference range, 1.0-6.5 μg/dl)
• ACTH-stimulated cortisol:  3.6 μg/dl (Reference range, 6.5-18.0 μg/dl)

We waited 3 weeks to do the second ACTH stimulation test which came in within the normal range. These results were as follows:

• Basal cortisol: 1.3 μg/dl  
• ACTH-stimulated cortisol:  9.5 μg/dl  

Based on this information, is it possible he has Addison's disease? Or is the fact that his stimulated cortisol value came back within the normal range on the second test just an indication that the prednisone was affecting the results in the first ACTH stimulation test?

I have been doing a lot of research on this because he seems to have many symptoms that match up with Addison's disease. Some things I've read have said that it is possible in atypical Addison's disease to have varying test results. Other things have disagreed. This is why I am trying to contact someone who specializes in this field. In your experience, is this something you have encountered?

I really appreciate any insight you may be able to give me. Thank you for your time.

My Response:

Causes of Hypoadrenocorticism in Dogs
In dogs, as in man, hypoadrenocorticism can be classified into primary and secondary subtypes (1-6). With primary hypoadrenocorticism, the primary disease process is in the adrenal glands themselves. In secondary hypoadrenocorticism, the problem lies in the pituitary gland where ACTH is secreted; with secondary forms of the disease, the cortisol secretion goes down because of too little ACTH secretion from the pituitary gland.

The most common cause of secondary hypoadrenocorticism is iatrogenic (induced inadvertently by the veterinarian) resulting from overly rapid discontinuation of long-term and/or high-dose glucocorticoid therapy. Very rare spontaneous or natural causes in the dog include pituitary or hypothalamic lesions (e.g., large destructive pituitary tumors) or idiopathic isolated ACTH deficiency.

In addition to primary Addison's disease or hypoadrenocorticism  (the failure of the adrenal glands to produce both glucocorticoid and mineralocorticoid hormones), and secondary (which is the failure of the pituitary gland to secrete ACTH, a hormone which stimulates the adrenal glands), a third type of hypoadrenocorticism has been described — "atypical" Addison's disease (7-9). This is a confusing term, which I believe can and should not be avoided because it really does not describe a definitive diagnosis.

Almost all of these dogs diagnosed with atypical Addison's can be classified into primary or secondary forms of the disease with proper diagnostic testing (10-11). In addition to ACTH stimulation testing, this may include  determination of circulating ACTH concentrations (the pituitary hormone). In some dogs, repeating the ACTH stimulation test and measuring the basal and ACTH-stimulated concentrations of aldosterone, a mineralocorticoid hormone is helpful.  Properly classifying the dogs into primary and secondary subtypes helps us better predict the needs for long-term treatment.

In  this dog, there is no reason to go any further because the last ACTH stimulation test completely rules out all forms of Addison's disease — primary, secondary, and atypical hypoadrenocorticism (see below).

ACTH Stimulation Testing
In normal dogs, administration of a dose of ACTH generally produces a rise in serum cortisol to values greater than 6 μg/dl. In contrast, dogs with hypoadrenocorticism (typical or atypical Addison's disease) have an absent or blunted response to ACTH administration. Basal and post-ACTH serum cortisol concentrations are less than 1 μg/dl in over 75% of dogs and less than 2 μg/dl in virtually all dogs with primary hypoadrenocorticism (1-6).

Although the post-ACTH serum cortisol concentration may be as high as 2 to 3 μg/dl in a few dogs with naturally occurring secondary hypoadrenocorticism (due to pituitary ACTH deficiency), the great majority of these dogs also have ACTH-stimulated cortisol concentrations of less than 2 μg/dl.

When borderline results occur (post ACTH cortisol concentrations between 2 and 6 μg/dl), the first thing that one must consider is the recent use of glucocorticoids, which would act through the negative-feedback effect to suppress circulating ACTH and cause temporary and mild atrophy of the adrenal cortical cells that secrete cortisol. That is likely what happened in your dog.

My Bottom Line

So in your dog, the first ACTH stimulation test is borderline for Addison's, but the cortisol response is high enough to make it unlikely. Remember that the dose given for Addison's disease would only be between 2.5-5 mg per day (around 0.1 mg/kg/day), so anything higher than that dose would suppress pituitary ACTH secretion and could lead to blunting of the cortisol response.

In accord with that, his second ACTH stimulation test done 3 weeks later is completely normal, totally excluding Addison's disease.

It's time to look for another disease. Consider an abdominal ultrasound or endoscopy next to better define your dog's gastrointestinal disease.

References:

1. Church DB. Canine hypoadrenocorticism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. 3rd ed. Quedgeley, Gloucester: British Small Animal Veterinary Assoc, 2004; 172-180.
2. Feldman EC, Nelson RW. Hypoadrenocorticism (Addison’s disease). In: Canine and Feline Endocrinology and Reproduction, 3rd ed. Philadelphia: Saunders, 2004; 394-439.  
3. Kintzer PP, Peterson ME. Primary and secondary canine hypoadrenocorticism. Veterinary Clinics of North American Small Animal Practice 1997;27:349-357. 
4. Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism: 225 cases (1979-1993). Journal of the American Veterinary Medical Association 1996; 208: 85-91.
5. Klein SC, Peterson ME. Canine hypoadrenocorticism: part I. Canadian Veterinary Journal 2010;51:63-69.
6. Klein SC, Peterson ME. Canine hypoadrenocorticism: part II. Canadian Veterinary Journal 2010;5:179-184.
7. Bartges JW, Nielson DL. Reversible megaesophagus associated with atypical primary hypoadrenocorticism in a dog. Journal of the American Veterinary Medical Association 1992; 201: 889-891.
8. Lifton SJ, King LG, Zerbe CA. Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995).  Journal of the American Veterinary Medical Association1996;209:2076-2081. 
9. Sadek D, Schaer M. Atypical Addison’s disease in the dog: A retrospective survey of 14 cases. J Am Anim Hosp Assoc 1996;32:159-163. 
10. Mueller C, Boretti FS, Wenger M, et al. Investigation on the aldosterone concentration before and after ACTH application in 44 dogs with hypoadrenocorticism. Kleintierpraxis 2007;52:216-224.
11. Insights into Veterinary Endocrinology Blog. Atypical Addison's Disease in Dogs with Gastrointestinal Signs. April 14, 2011.

Watch Out for Canine Addison's Disease

Dr. Peterson's expertise in veterinary endocrinology was tapped by Dog Fancy Magazine to provide professional insight into the diagnosis and treatment of Addison's disease.

This article was a part of the monthly "Watch Out For" feature which gives an overview of common diseases and medical conditions, with Dr. Peterson's Addison's disease article appearing in the October issue.

Can Chronic Stress and Cortisol Resistance Make Your Pet Sick?

It is well known that chronic stress and illness are related. For example, psychological stress in humans raises the risk of heart disease, colds and flu. And chronic stress in animals is also well known to lead to diseases such as upper respiratory or lower urinary tract infections.

But how does such stress lead to illness? New research published recently in the Proceedings of the National Academy of Sciences (1) found that the adrenal hormone cortisol plays a critical role in the illness caused by stress.

Released in greater amounts in times of stress, cortisol helps suppress the body’s immune response to infections, suppressing inflammation responses like coughing, sneezing, or fever. But when levels of cortisol remain high, the body may become less sensitive to it — a condition called cortisol or glucocorticoid "resistance."

So in other words, when we are stressed out, we overproduce cortisol, making our immune system incapable of turning "off" the inflammation response. If we're exposed to a virus while we are also dealing with chronic stress, the study found that we'd also be much more likely to get sick and suffer from more intense symptoms (1).

In other words, many of the symptoms of a cold, for example, are not caused directly by the virus, but rather, they're caused by the inflammatory response to the infection. We want the body to produce enough of inflammation to fight off the infection, but not so much that we experience worsened symptoms.

The Bottom Line:
Chronic stress may raise the risk of sickness by creating a state of resistance to the hormone cortisol, which, in turn, interferes with appropriate regulation of inflammation.  Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.

Although we do no know if the same phenomenon of stress-induced cortisol resistance exists in animals, it is certainly possible. We certainly do know that physical and psychological stress can induce disease in domestic animals (2-4).

References:

1. Cohen S, Janicki-Deverts D, Doyle WJ, et al.  Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk.  Proceedings of the National Academy of Sciences (PNAS) 2012; ,doi:10.1073/pnas.1118355109.
2. Westropp JL, Kass PH, Buffington CA. Evaluation of the effects of stress in cats with idiopathic cystitis. American Journal of Veterinary Research 2006;67:731-6.
3. McCobb EC, Patronek GJ, Marder A, et al. Assessment of stress levels among cats in four animal shelters. Journal of the American Veterinary Medical Association 2005;226:548-555.
4. Stephens DB. Stress and its measurement in domestic animals: a review of behavioral and physiological studies under field and laboratory situations. Advanced in Veterinary Science and Comparative Medicine 1980;24:179-210.

Hypoadrenocorticism (Addison’s Disease) in Cats

Hypoadrenocorticism, also called adrenal insufficiency or Addison’s disease, is a disorder in which the adrenal gland does not produce sufficient adrenal hormones that are essential for life.  When the adrenal glands fail, the consequences are very severe. Untreated, hypoadrenocorticism may lead to death.

Fortunately, naturally occurring hypoadrenocorticism is extremely rare in cats, with less than 25 cases reported. However, the disease is generally missed because veterinarians rarely consider this problem as a differential diagnosis in cats.

A much more common reason that cats develop hypoadrenocorticism is long-term treatment with steroids for a variety of dermatologic or behavioral reasons. These cats do not show signs of adrenal insufficiency unless the mediation is stopped too abruptly. This is also known as iatrogenic hypoadrenocorticism (see, "What causes this disease in cats," below).

What are the missing hormones in cats with hypoadrenocorticism?

Like dogs or people with Addison’s disease, cats with hypoadrenocorticism are unable to produce one or two steroid hormones, both secreted from the adrenal cortex (outer layer of the adrenal gland).

1. The first hormone that's missing is cortisol, which is very important in maintaining a normal metabolism, as well as a general sense of well-being.
2. The second hormone that's missing is aldosterone, which manages the water balance and serum electrolytes in the body.

What are the different forms of hypoadrenocorticism in cats?

Hypoadrenocorticism can be divided into primary and secondary subtypes:

• With primary hypoadrenocorticism (Addison's disease), the problem lies in the adrenal gland itself, with atrophy or destruction of the gland.
• With secondary hypoadrenocorticism, the adrenal glands are normal, and the problem lies in the pituitary gland. The pituitary gland normally secretes a hormone called ACTH (adrenocorticotropic hormone) that stimulates the adrenal gland to secrete its hormones. In secondary hypoadrenocorticism, ACTH is not secreted in needed amounts, leading to the secondary adrenal insufficiency.

What causes this disease in cats?

In most cats with naturally occurring hypoadrenocorticism, the exact cause for the adrenal failure is never known for certain.  

Many cats, however, develop the problem because of iatrogenic causes. The term iatrogenic means that the disease is caused by, or results from, a medical or surgical treatment for another problem (i.e., the disease did not develop spontaneously).  

In cats with primary hypoadrenocorticism, the following causes must be considered.

• Most cats that develop Addison’s disease spontaneously appear to have an autoimmune condition in which the body destroys part of the adrenal cortex.
• Infiltrative conditions such as lymphoma (a form of cancer) can destroy the adrenal gland to cause Addison’s disease.
• Surgical removal of both adrenal glands for treatment of feline Cushing’s disease will result in iatrogenic Addison’s disease, but this is a rarely used operation for cats.  
• Rarely, primary adrenal failure can occur secondary to trauma. This may be temporary or permanent.

In cats with secondary hypoadrenocorticism, the following underlying causes should be excluded. Again, all of these conditions are associated with deficient secretion of the pituitary hormone, ACTH.

• Congenital deficiency of ACTH secretion (not yet reported in cats).
• Pituitary tumors, inflammation, or trauma that have destroyed most of the ACTH-secreting cells in the pituitary gland, leading to deficient ACTH secretion.
• Iatrogenic hypoadrenocorticism that results from administration of large doses of cortisone-like hormones (glucocorticoids or progesterone-like drugs), which are then withdrawn too rapidly. In this case, the term iatrogenic means that the hypoadrenocorticism is caused by the high-dose glucocorticoid or progestin (megestrol acetate; trade names, Ovaban or Megace) treatment.   

Chain of events leading to severe hypoadrenocorticism in cats

With primary hypoadrenocorticism (Addison's disease), cats develop complete adrenocortical destruction with both cortisol and aldosterone deficiencies.

Aldosterone is the main mineralocorticoid hormone, and it affects the levels of potassium, sodium, and chloride in the blood. Low levels of aldosterone cause potassium to gradually build up in the blood and, in severe cases, cause the heart to slow down or beat irregularly. Some cats have such a slow heart rate (50 beats per minute or lower) that they can become weak or go into shock.

More commonly, cats will develop iatrogenic, secondary hypoadrenocorticism (see above, What causes this disease in cats) to treatment with steroid-like drugs used for anti-inflammatory purposes. This subgroup of hypoadrenal cats is only deficient in cortisol and maintains a normal aldosterone level. These cats are more difficult to diagnose because their signs are milder and the serum potassium, sodium, and chloride values all remain normal.

What are the clinical signs and symptoms of feline hypoadrenocorticism?

Signs of hypoadrenocorticism may include repeated episodes of vomiting and diarrhea, loss of appetite, dehydration, and gradual, but severe, weight loss.

Because the clinical signs of hypoadrenocorticism are vague and nonspecific, it can be difficult to diagnose in the earlier stages of disease. Therefore, severe consequences, such as shock and evidence of kidney failure, can develop suddenly in some cats with complete adrenocortical destruction.

In cats with secondary hypoadrenocorticism, the clinical signs generally are not as severe and are usually not life threatening.

How is feline hypoadrenocorticism diagnosed? 

A veterinarian may suspect hypoadrenocorticism based on the cat’s history (including past treatment with steroids or progestins), clinical signs, and certain laboratory abnormalities, such as low serum sodium and high potassium concentrations. However, one must specifically evaluate adrenal function to document low cortisol levels to definitively diagnose hypoadrenocorticism.

The diagnosis of hypoadrenocorticism is confirmed by lack of cortisol response to ACTH administration. It is important to recognize that the reference range for the post ACTH cortisol is lower in cats than in dogs. To confirm a diagnosis of hypoadrenocorticism, however, the serum concentrations of both the basal cortisol level and ACTH-stimulated cortisol levels are low (generally less than 2 μg/dl).   

How is primary hypoadrenocorticism (Addison’s disease) treated?

Untreated, primary hypoadrenocorticism (Addison’s disease) can lead to an adrenal crisis.  An adrenal crisis is a medical emergency that requires intravenous fluids to restore the body’s levels of fluids, salts, and sugar to normal.  Once stabilized, the cat can then be treated with hormone replacement therapy (either orally or by injection).  With proper treatment, the long-term prognosis is excellent.

Long-tem treatment of primary hypoadrenocorticism (Addison’s disease) includes treatment with either both missing adrenal hormones.  For mineralocorticoid replacement, either oral fludrocortisone (trade name, Florinef) or injectable desoxycortisone privalate (DOCP, trade name, Percorten) are given. In cats, glucocorticoid replacement is best given as oral or injectable prednisolone.   

Response to treatment is similar although clinical signs such as anorexia, lethargy, and weakness may sometimes take longer to resolve than in dogs. Prognosis for long-term survival is good with the exception of cats in which the underlying cause is adrenal neoplasia.

How is iatrogenic hypoadrenocorticism (secondary to overtreatment with steroids or progestins) treated?

In cats with iatrogenic hypoadrenocorticism due to overtreatment with steroids for nonendocrine problems, treatment simply involves reinstituting glucocorticoid replacement at a gradual tapering dosage over weeks to months. This allows the pituitary ACTH-secreting cells to recover and stimulate normal cortisol secretion once again.

Treating Dogs with Hypoadrenocorticism (Addison's Disease)

Addison's disease, the common name for hypoadrenocorticism or adrenal insufficiency, as I have discussed in my last two blog posts, is a disease with vague clinical features that are common in many other ailments, making diagnosis difficult in many cases. But once Addison's disease is correctly diagnosed, a properly treated dog can live a normal and happy active life.

The missing adrenal hormones

The adrenal, one on each kidney, is made up of two layers, the cortex and the medulla. The inner medulla secretes epinephrine (adrenaline) and is not affected by Addison's disease. The outer cortex layer secretes two corticosteroid hormones, cortisol and aldosterone, both of which are deficient in Addison's disease.

Aldosterone is a corticosteroid hormone (more specifically, a mineralocorticoid — think minerals: salt, sodium, potassium) responsible for maintaining normal circulating electrolyte levels. Once secreted, aldosterone acts on the kidney to conserve sodium, excrete potassium, and retain needed water.

Cortisol is also a corticosteroid hormone (in this case, a glucocorticoid — think glucose, sugar, energy) that is essential for life. It supports a variety of important cardiovascular, metabolic, immunologic, and stress functions.

Not all forms of hypoadrenocorticism are treated the same
There are three forms of hypoadrenocorticism: primary, secondary and atypical Addison's disease.

1. Primary Addison's disease is most commonly is the result of immune-mediated damage to the glands.
2. Atypical Addison's disease is a poorly understood disorder, thought to generally be an early stage of primary Addison's disease.
3. Secondary hypoadrenocorticism results from a deficiency of the pituitary hormone, adrenocorticotropic hormone (ACTH). Without circulating ACTH, cortisol cannot be secreted by the adrenal glands.

It is important which form of hypoadrenocorticism is present in order to provide the correct treatment. In primary hypoadrenocorticism, both cortisol and aldosterone are deficiency and must be replaced for life. In atypical and secondary hypoadrenocorticism, on the other hand, only the glucocorticoids need to be replaced, at least initially.

Treating the acute adrenal crisis: A true medical emergency
Untreated, hypoadrenocorticism (especially primary Addison's disease) can lead to an adrenal crisis. An adrenal crisis is a medical emergency that requires intravenous fluids and glucocorticoids to restore the body’s levels of fluids, salt, and sugar to normal.

Once stabilized, the dog can then be treated with glucocorticoid and mineralocorticoid replacement therapy at home.

Treating chronic hypoadrenocorticism: A lifelong disease
Depending of the subtype of hypoadrenocorticism, synthetic corticosteroid drugs that act like mineralocorticoid or glucocorticoids used for hormone replacement therapy.

Mineralocorticoid treatment

For mineralocorticoid (aldosterone) replacement, either an oral medication called fludrocortisone acetate (Florinef™) or the injectable desoxycorticosterone pivalate (DOCP; Percorten-V™) is used.

We typically institute treatment with DOCP (Percorten-V) at a dosage of 2.2 mg/kg, subcutaneously or intramuscularly, every 25 to 30 days. Side effects associated with DOCP therapy are rare. This dosage interval is effective in almost all dogs, and most are well controlled with a DOCP injection every 4 weeks.

Initially, serum kidney and electrolyte concentrations should be monitored at approximately 2-weeks intervals in order to determine the drug’s peak effect and to help make necessary dosage adjustments. Once stabilized, serum electrolyte and creatinine concentrations are checked every 3 to 6 months. Because DOCP is a pure mineralocorticoid and has no glucocorticoid activity, it is essential that dogs receive concurrent glucocorticoid supplementation (see below).

Fludrocortisone is a synthetic corticosteroid that possesses moderate glucocorticoid activity as well as having marked mineralocorticoid potency. By comparison, fludrocortisone has 10 times the glucocorticoid activity and 125 times the mineralocorticoid activity of cortisol. In this regard, fludrocortisone is very different than DOCP, which possess no glucocorticoid activity.

If fludrocortisone acetate is employed as mineralocorticoid supplementation, we recommend an initial oral dosage of approximately 0.02 mg/kg/day.

After initiation of fludrocortisone therapy, serum electrolyte and creatinine concentration should be monitored weekly, with the dosage adjusted by 0.05-0.1 mg/day increments until values have stabilized within the reference range. Once this is achieved, the dogs should be reevaluated monthly for the first 3 to 6 months of therapy, then every 3 to 6 months thereafter.

For dogs that have atypical or secondary Addison’s, mineralocorticoid replacement therapy with DOCP or fludrocortisone aren't needed because the production of aldosterone isn’t effected and the serum electrolytes remain in balance.

Glucocorticoid treatment

In addition to replacing deficient mineralocorticoids in dogs with Addison's disease, the missing glucocorticoids must also be replaced. This is typically done with an oral form of the synthetic glucocorticoids prednisone, prednisolone, or hydrocortisone. With atypical Addison's and secondary forms of hypoadrenocorticism, glucocorticoid replacement is all that is needed, at least initially, since these dogs do not have serum electrolyte abnormalities.

 The correct dose of the supplemented glucocorticoids, such as prednisone, cannot be measured with a blood test. Rather it's determined by your observations: the lowest dose that keeps your dog symptom free, happy and eating! The most common side effect of overdosage is an increase in thirst and urination, which can be intense in some dogs.

Prognosis of Addison's disease

With proper treatment, the long-term prognosis is excellent. While your dog with Addison’s disease will need medications and monitoring for the rest of his life, most dogs with Addison’s can return to their favorite activities. You will help your dog lead a normal, active and fun-filled life.