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Author Topic: Primary Addison's Disease - updated, June 2016  (Read 1959 times)

Jo CIMDA

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Primary Addison's Disease - updated, June 2016
« on: June 13, 2016, 04:05:19 PM »

PRIMARY ADDISON’S DISEASE (HYPOADRENOCORTICISM)

The diagnosis of primary Addison’s disease is not complicated but some vets seem to have a reluctance even considering it in their differential diagnoses. It is often misdiagnosed as CRF (chronic renal failure), heart failure, gastrointestinal disease and even primary  autoimmune haemolytic anaemia (AIHA).  Many vets say “It won’t be Addison’s as we never see it”. Unless your vet is looking for Addison’s disease then it will not be diagnosed.  Addison’s disease is known as ‘The Great Pretender’. Many dogs are presented to their vet at least three times in the six months prior to diagnosis, and many are in an Addisonian crisis before it is identified.  Note: Dogs have died waiting for the results of an ACTH test through lack of supportive care. 

The biggest hurdle is to convince your vet to consider the possibility of your dog having Addison’s disease, and not to dismiss the notion without proving it and carrying out a thorough investigation and possibly an ACTH test. 

Even if your dog’s breed is known to be predisposed to Addison’s disease, it is important not to become too ‘Addisonian neurotic’ just because your dog has a bout of diarrhoea or an episode of being a little off colour, but it is equally important to be aware of the tell-tale signs which could aid a diagnosis and maybe save your dog’s life.

Clinical signs: 
Lethargy, depression, nervousness, weight loss, anorexia (no appetite), vomiting, weakness (particularly of the back legs), shaking or muscle tremors, limping, diarrhoea (with or without traces of blood), abdominal pain, dehydration, excessive thirst and urination, weak pulse, slow heart rate and abnormal heart rhythm, anaemia (pale gums) and collapse.

Points to consider when identifying primary Addison’s disease:
Is your dog young / middle aged?
Over a period of time, has your dog experienced several of the typical symptoms and has he/she responded well to fluid therapy?
Has your young to middle aged dog been diagnosed with kidney disease?  Is he/she improving on the special treatment/diet provided by your vet? If the answer is no, then consider Addison’s disease.
Do you have a dog whose breed is known to be genetically predisposed to Addison’s disease?
Do you know of any relatives of your dog who may have been diagnosed with Addison’s disease or kidney failure at a young age, or other autoimmune disease? Speak to your dog’s breeder; they may be able to give you valuable information.

If you suspect Addison’s disease
Have a Full Serum Biochemistry panel and a Complete Blood Count test done and ask your vet for a copy of the results for your own records.  Study the results yourself and note any abnormalities. If symptoms persist, have a further blood test done to see if there are any changes, but don’t leave it too long in between (a week or less) as deterioration seems to quicken in the last stages.  Keep all laboratory reports for comparison in the future. Blood testing is never a waste of money (in the long term it can save you money), and it provides a ‘bench mark’ on which to compare further tests.  Addison’s disease is progressive so a blood test is only valid at the time it was taken.  As the disease process progresses the values will change.

The tell-tale signs when looking at blood test results

Routine Laboratory Abnormalities  -  Haematology & Biochemistry

Sodium/Potassium Ratio

Greater than 90% of Primary Addisonian cases will have low sodium (Na) and high potassium (K) values, with a ratio of less than 27.  (Na:K)
Prior to diagnosis, Addisonian dogs often show a ratio of less than 23. The low ratio alone is very suggestive, but not diagnostic, of Addison’s disease. Individual electrolyte concentrations can be more reliable.

As the disease progresses, the ratio will drop even further and the dog may collapse and become critically ill, especially if stressed or excited.  Stress or excitement, to a dog with reduce adrenal function (even in one who has not exhibited typical, clinical signs of Addison’s disease), can cause the dog to collapse or even die suddenly.

When comparing laboratory results look for the following as these will indicate Addison’s disease.

INCREASED: 

High Potassium (K)
High Creatinine,
High Urea, (BUN – blood urea nitrogen; or SUN - serum urea nitrogen)
High Urea/creatinine ratio (Azotaemia)
Increased Eosinophils
Increased Lymphocytes
High Bilirubin -  in some cases
High Calcium (mild to moderate) – in some cases
ALT- ALP - AST (Mild to moderate increase of liver enzymes) – in some cases

DECREASED:

Low Sodium (Na)
Low Sodium/potassium ratio (K:Na ratio -  less than 27)
Note: Addisonian dogs often have a ratio of <23
Low Chloride  (80% of Addisonian dogs will have low chloride values)
Low Glucose – in some patients
Low Albumin (moderate to severe) – in some cases
Total white blood cell count (WBC) – in some cases
Red blood cell count (RBC or HCT)

Another possible difference between kidney disease and Addison’s may be seen in the white blood cells (eg., neutrophils, eosinophils, lymphocytes). When a dog is ill (but does not have Addison’s disease) he becomes stressed and this is often reflected in the white cells. The neutrophil numbers are expected to be high normal to increased, and the eosinophils and lymphocytes numbers are low normal to decreased. This is called ‘stress leucogram’ and is seen in both chronic and acute renal failure, but not in Addison’s disease.

 A dog with Addison’s disease may show a different white cell reading than would be expected in such an ill dog.  In fact there may even be reverse of what would normally be expected, known as ‘reverse stress leucogram’.

Reverse Stress Leucogram – may be seen in Addisonian dogs

Low normal numbers of neutrophils
Increased numbers lymphocytes and eosinophils


Electrocardiogram


•   Electrocardiogram  (ECG) is a very useful tool to detect various abnormalities of the heart resulting from high potassium levels in the blood.
Another very awkward differential is autoimmune haemolytic anaemia (AIHA).  I have known a few dogs to be diagnosed with AIHA prior to being diagnosed with Addison’s disease. The usual treatment for AIHA had been implemented but the dog’s clinical signs did not improve as expected, and clinical signs of Addison’s disease, remained. 

If this happens you should check for signs of Addison’s on previous blood test results to see if there were any undetected tell-tale results such as high potassium, low sodium.   These cases are further complicated because of the steroid treatment the dog will now be receiving for AIHA. A diagnostic ACTH test cannot be performed whilst a dog is on prednisolone, as it will interfere with the test results, so the dog’s medication would have to be changed to dexamethasone for at least 2-3 days before an ACTH test is performed.

Prompt diagnosis and treatment, or supportive treatment, is crucial to the outcome of an Addisonian crisis and must be treated as a true emergency if the dog is to survive.

Life saving support

From BSAVA Manual of Small Animal Endocrinology, Chapter 19 – Endocrine Emergencies

“Whenever a diagnosis of Addisonian crisis is likely, treatment should be initiated without delay.” 
“A tentative diagnosis of acute adrenocortical insufficiency can be made on the basis of the history and results of physical examination.”
“Since death from acute adrenocortical insufficiency is usually attributed to vascular collapse and shock, rapid correction of hypovolaemia is the first priority in treating this condition.”


1.   Restoring blood volume and
2.   Correcting imbalance of sodium and potassium levels and
3.   Treatment of life threatening cardiac arrhythmias

Within 1-2 hours, a saline only intravenous drip can restore correct hydration status, increase sodium levels and lower potassium levels which may be causing hyperkalaemic myocardial toxicity. In addition, other protocols may be used if myocardial toxicity is life threatening.

4.   Correct glucocorticoid deficiency

Dexamethasone is usually given to correct glucocorticoid deficiency as this has little or no effect on the measurement of endogenous cortisol concentrations and therefore does not interfere with the ACTH test.

Zycortal Treatment


Once diagnosis is achieved, the prognosis for an Addisonian dog is excellent. The dog should feel much better in a few days but it may take up to 6-8 weeks after the start of treatment for the clinical signs and blood results to return to normal.

Since April 2016, the treatment for Addison’s disease in the UK has changed from a daily mineralocorticoid tablet (with some glucocorticoid  hormone included), to an injectable mineralocorticoid called Zycortal, given approximately once every month, depending on clinical signs and monitoring of sodium and potassium values. The duration of time between Zycortal injections appears to vary from one individual to another.  There are many reports suggesting that the recommended manufacturer’s dose of 2.2mg/kg is much higher than needed, and care must be taken not to overdose.

Please see these links:

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c9b766a-c36b-44aa-bbd8-24fab24ca97c

http://www.endocrinevet.info/2011/11/q-prolonged-action-of-percorten-in-dog.html

www.addisondogs.com/addisons/articles/julia_bates_interview_2012.pdf

http://www.ncbi.nlm.nih.gov/pubmed/23438457

A daily dose of prednisolone, to replace glucocorticoid deficiency, will also be necessary when a dog is being treated with Zycortal.  Replacement dose for glucocorticoid deficiency in an Addisonian dog is prednisolone  0.2–0.3mg/kg once a day (BSAVA Small Animal Formulary 6th Edition). This dose may need to be increased at times of stress because an Addisonian dog no longer has the ‘supply and demand’ facility for the ‘fight/flight’ response at times of stress.  It might be prudent for the owner to anticipate added stress such as a brewing thunderstorm or kennelling etc.

Life-long, daily glucocorticoid hormone replacement therapy is essential alongside regular subcutaneous injections of Zycortal.

Zycortal is expected to suit approximately 80% of Addisonian dogs, but those who fail to stabilise on Zycortal will have to revert to treatment with Florinef. See information below.

Florinef is a daily replacement mineralocorticoid hormone tablet (with some glucocorticoid activity) called fludrocortisone (Florinef). Tablets should be given regularly, around the same time/times every day.  Initially, Florinef will be given with the addition of another hormone tablet called prednisolone.  Prednisolone is a glucocorticoid hormone.

Note: Although Addison’s disease is easy to treat with Florinef, daily medication is essential.  Missing one or two doses of Florinef is not an option and it could prove to be fatal.
 
Florinef Treatment

Drugs & Dosage: 

Extract from BSAVA Small Animal Formulary, 6th Edition

For mineralocorticoid supplementation in chronic or subacute adrenal insufficiency:
Fludrocortisone (Florinef) Oral: 0.1mg tablet

Initial dose: Start at 0.01mg/kg 24 hrs depending on size of animal.  Monitor sodium and potassium levels every 1-2 weeks and adjust dose by 0.05 – 0.1mg accordingly.  Most patients once stabilised will require approx. 0.1mg/5kg 24hrs.

For glucocorticoid supplementation in chronic or subacute adrenal insufficiency:

Prednisolone:  0.2-0.3mg/kg given once daily with fludrocortisone.  The use of prednisolone may be discontinued in most cases once the animal is stable.

Useful References:

“When the disease is first diagnosed, a higher dose of prednisolone is often necessary (up to 0.5mg/kg every 12 hours) but should be tapered rapidly to the lowest amount”. Ref: Unmasking the Great Pretender’: how to recognise and manage canine Addison’s disease by Audrey Cook BVM&S MRCVS Dip ACVIM-SAIM Dip ECVIM-CA.

‘Most dogs can be successfully treated on once daily therapy but some will require twice daily treatment to maintain electrolyte concentrations within reference ranges. Fludrocortisone possesses a small degree of glucocorticoid activity and therefore also assists in weaning affected dogs off prednisolone therapy. The dosage of Fludrocortisone increases with time for reasons that are yet unclear and many dogs subsequently require doses as high as 0.03 mg/kg/day’. Ref: FECAVA Lecture Addison’s Disease (Hypoadrenocorticism) in Dogs – Carmel T Mooney

Note:  Florinef should be kept cool and stored in a fridge.

A gastroprotectant may be given if gastrointestinal bleeding is present.

Following replacement hormone treatment with Florinef and prednisolone, the dog should feel much better in a few days, but it may take up to 6-8 weeks for the clinical signs and blood results to return to normal. The optimum dose of Florinef is established during this time and several blood tests, to check that the sodium and potassium ratio is back within normal range, are necessary and should be performed weekly from the start of treatment.
The oldest dog with Addison’s that I have known was over 16 years old when she died, so getting that diagnosis is worth fighting for.

For more information about Addison’s Disease and treatment, please see the following link:

http://www.addisondogs.com/support/
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